MedWorm: Stem Cell Therapy

Eclipse Therapeutics Appoints Hans Clevers, M.D., Ph.D., and Thomas...

PRWeb: Medical Pharmaceuticals — Fri, 03 Feb 2012 06:24:02 +0100

Eclipse Therapeutics, Inc., a biotechnology company dedicated to the discovery and development of novel therapeutics that target cancer stem cells, announced today the appointments of Hans Clevers,...(PRWeb February 01, 2012)Read the full story at http://www.prweb.com/releases/2012/2/prweb9155733.htm (Source: PRWeb: Medical Pharmaceuticals)

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An osteosarcoma zebrafish model implicates Mmp‐19 and Ets‐1 as well as reduced host immune response in angiogenesis and migration

The Journal of Pathology — Fri, 03 Feb 2012 05:32:13 +0100

AbstractAbout 40% of osteosarcoma patients die of metastases. Novel strategies to improve treatment of metastatic patients require a better understanding of the processes involved, like angiogenesis, migration and the immune response. However the rarity of osteosarcoma and its heterogeneity make this neoplasm difficult to study. Recently we reported malignant transformation of mouse mesenchymal stem cells (MSCs) which formed osteosarcoma upon transplantation into mice. Here we studied these cells in zebrafish embryos and found that transformed MSCs induced angiogenesis and migrated through the bodies of the embryos, but this was never observed with non‐transformed normal MSCs (progenitors of the transformed MSCs). Whole genomic expression analysis of both the cells and the host showed th...

Hematopoietic stem cell engineering at a crossroads

Blood — Thu, 02 Feb 2012 05:00:00 +0100

The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave o...

High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement

Blood — Thu, 02 Feb 2012 05:00:00 +0100

High-dose melphalan (HDM) plus stem cell transplantation is an effective treatment for light-chain amyloidosis (AL), but is associated with high treatment-related mortality in patients with cardiac involvement. We studied 187 patients with cardiac involvement with AL who underwent HDM between 1996 and 2008. The median age was 57 years and the median time from diagnosis to HDM was 3.6 months. Half of the patients received reduced-dose melphalan (100-160 mg/m2). The median overall survival (OS) was 66 months, 54 months from diagnosis and HDM, respectively, and 91 patients (49%) were alive at the last follow-up 52 months (median) from HDM. Thirty patients (16%) died within 100 days of transplantation; only low serum albumin predicted early deaths. Overall, hematologic response (HR) and cardia...

A novel lentiviral vector targets gene transfer into human hematopoietic stem cells in marrow from patients with bone marrow failure syndrome and in vivo in humanized mice

Blood — Thu, 02 Feb 2012 05:00:00 +0100

In conclusion, this new LV will facilitate HSC-based gene therapy by directly targeting these primitive cells in BM aspirates or total cord blood. Most importantly, in the future, RDTR/SCF-LVs might completely obviate ex vivo handling and simplify gene therapy for many hematopoietic defects because of their applicability to direct in vivo inoculation. (Source: Blood)

ECSASB2 mediates MLL degradation during hematopoietic differentiation

Blood — Thu, 02 Feb 2012 05:00:00 +0100

Mixed lineage leukemia (MLL) is a key epigenetic regulator of normal hematopoietic development and chromosomal translocations involving MLL are one of the most common genetic alterations in human leukemia. Here we show that ASB2, a component of the ECSASB E3 ubiquitin ligase complex, mediates MLL degradation through interaction with the PHD/Bromodomain region of MLL. Forced expression of ASB2 degrades MLL and reduces MLL transactivation activity. In contrast, the MLL-AF9 fusion protein does not interact with ASB2 and is resistant to ASB2 mediated degradation. Increased expression of ASB2 during hematopoietic differentiation is associated with decreased levels of MLL protein and down-regulation of MLL target genes. Knockdown of ASB2 leads to increased expression of HOXA9 and delayed cell di...

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A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside

Blood — Thu, 02 Feb 2012 05:00:00 +0100

Gene regulatory networks that govern hematopoietic stem cells (HSCs) and leukemia-initiating cells (L-ICs) are deeply entangled. Thus, the discovery of compounds that target L-ICs while sparing HSC is an attractive but difficult endeavor. Presently, most screening approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPCs). Here, we present a multistep in vitro and in vivo approach to identify compounds that can target L-ICs in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which 10 were less toxic to HSPC. We characterized a single compound, kinetin riboside (KR), on AML L-ICs and HSPCs. KR demonstrated comparable effic...

Predictive factors for inadequate stem cell mobilization in Chinese patients with NHL and HL: 14‐year experience of a single‐center study

Journal of Clinical Apheresis — Thu, 02 Feb 2012 05:00:00 +0100

Conclusion: Our analysis showed that high amounts of chemotherapy, radiotherapy, low platelet count, chemosensitive recurrent patients, combination chemotherapy plus G‐CSF and low CD34+ cells in BM prior to mobilization could emerged as important predictive factors for mobilization failure in Chinese patients with NHL and HL. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc. (Source: Journal of Clinical Apheresis)

Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis

Journal of Hematology and Oncology — Thu, 02 Feb 2012 05:00:00 +0100

Conclusions: Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery. (Source: Journal of Hematology and Oncology)

Encouraging stem cell results

Multiple Sclerosis Trust — Thu, 02 Feb 2012 00:00:00 +0100

Results from a small study published in Lancet Neurology suggest that stem cells may protect nerves from MS related damage. (Source: Multiple Sclerosis Trust)

Children’s becomes first hospital in New England to complete six organ transplant

Thrive, Children's Hospital Boston — Wed, 01 Feb 2012 15:57:55 +0100

The cover of today’s Boston Globe features the beaming face of Alannah Shevenell, a 9 year-old who will be heading home to Maine this morning after a three-month stay at Children’s Hospital Boston. For just under 100 days Alannah and her grandmother have been staying at Children’s while she received treatment for a rare and aggressive cancer that was compromising several of her internal organs. When all other treatments had failed, Heung Bae Kim, MD, director of Children’s Pediatric Transplant Center (PTC), suggested a multivisceral transplant that would remove Alannah’s tumor and replace the six organs that had been damaged by its presence. Under Kim’s guidance surgeons from Children’s PTC performed the 14-hour procedure. Once Alannah’s tumo...

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Stanford Scientists Turn Skin Cells Into Neural Precusors, Bypassing Stem-Cell Stage

Health News from Medical News Today — Wed, 01 Feb 2012 08:00:00 +0100

Mouse skin cells can be converted directly into cells that become the three main parts of the nervous system, according to researchers at the Stanford University School of Medicine. The finding is an extension of a previous study by the same group showing that mouse and human skin cells can be directly converted into functional neurons. The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another... (Source: Health News from Medical News Today)

Stem Cell Therapy Shows Promise for Stroke, Studies Say

MedicineNet Cancer General — Wed, 01 Feb 2012 07:00:00 +0100

Title: Stem Cell Therapy Shows Promise for Stroke, Studies SayCategory: Health NewsCreated: 2/1/2012 10:06:00 AMLast Editorial Review: 2/1/2012 (Source: MedicineNet Cancer General)

MIT: Stem cells could drive hepatitis research forward

EurekAlert! - Medicine and Health — Wed, 01 Feb 2012 05:00:00 +0100

(Massachusetts Institute of Technology) Researchers produce liver-like cells from induced pluripotent stem cells. By creating liver-like cells, scientists can study why people respond differently to Hepatitis C. (Source: EurekAlert! - Medicine and Health)

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[Comment] PTLD treatment: a step forward, a long way to go

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of diseases that develop as a consequence of immunosuppression in patients who have undergone solid-organ or haemopoietic-stem-cells transplantation. PTLDs include a series of disorders ranging from Epstein-Barr virus (EBV)-driven polyclonal proliferation to disorders indistinguishable from some B-cell lymphomas or, less often, T-cell lymphomas. Although the diagnosis can be suspected by clinical features (ie, lymphadenopathy), serum markers (ie, increasing concentrations of serum lactate dehydrogenase), imaging studies, and an increase in the EBV viral load, definitive diagnosis eventually relies on tissue biopsy. (Source: The Lancet Oncology)

[Comment] Renaissance of autologous stem cell transplantation for AML?

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

After intensive induction chemotherapy, 70–80% of young adult patients with newly diagnosed acute myeloid leukaemia (AML) achieve complete remission (CR); however, without additional treatment, most will relapse within a few months. Accordingly, the aim of post-remission treatment (PRT) is to eradicate residual disease, which persists after induction and is not detectable at examination of the bone marrow morphology. (Source: The Lancet Oncology)

[News] Arrests in USA over unapproved stem-cell therapies

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Federal investigators in the USA have charged four men with defrauding patients with terminal diseases by selling them unapproved stem-cell therapies. Among those arrested was Vincent Dammai, a cellular biologist and cancer researcher at the Medical University of South Carolina (Charleston, SC, USA). Dammai is charged with producing stem-cell lines for the scheme using university equipment; Dammai was placed on administrative leave and his laboratory was secured for investigators, university officials told The Lancet Oncology. (Source: The Lancet Oncology)

[Personal View] The developing cancer stem-cell model: clinical challenges and opportunities

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

During the past decade, a stem-cell-like subset of cancer cells has been identified in many malignancies. These cells, referred to as cancer stem cells (CSCs), are of particular interest because they are believed to be the clonogenic core of the tumour and therefore represent the cell population that drives growth and progression. Many efforts have been made to design therapies that specifically target the CSC population, since this was predicted to be the crucial population to eliminate. However, recent insights have complicated the initial elegant model, by showing a dominant role for the tumour microenvironment in determining CSC characteristics within a malignancy. (Source: The Lancet Oncology)

Acute Lymphoblastic Leukemia: Monitoring Minimal Residual Disease as a Therapeutic Principle

Seminars in Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Measurement of submicroscopic (minimal) levels of residual disease (MRD) can be used to monitor treatment response much more precisely than morphological screening of bone marrow slides. Several studies have demonstrated that MRD assessment in childhood and adult acute lymphoblastic leukemia (ALL) significantly correlates with clinical outcome. MRD detection is particularly useful for evaluation of early treatment response, but also to monitor disease before and after stem cell transplantation, for early assessment of an impending relapse and in the setting of salvage treatment. Currently, three highly specific and sensitive methodologies for MRD detection are available, namely, real-time quantitative polymerase chain reaction (RQ-PCR) of fusion gene transcripts or breakpoints, RQ-PCR–ba...

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Chronic Myeloid Leukemia: Clinical Impact of BCR-ABL1 Mutations and Other Lesions Associated With Disease Progression

Seminars in Oncology — Wed, 01 Feb 2012 05:00:00 +0100

The introduction of the tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, and nilotinib has dramatically improved the treatment of chronic myeloid leukemia (CML). However, a minority of CML patients in chronic phase (CP) and a substantial proportion of patients in advanced phase are either initially refractory to TKIs or eventually develop resistance. Rates of resistance and relapse directly correlate with disease progression. The most frequently identified mechanism of acquired TKI resistance is BCR-ABL1 kinase domain (KD) mutations that impair TKI binding by disrupting the drug contact sites or causing conformational changes that make the contact sites inaccessible. The underlying mechanisms of disease progression are heterogeneous and only poorly understood. So far the most frequen...

p53-Independent, Normal Stem Cell Sparing Epigenetic Differentiation Therapy for Myeloid and Other Malignancies

Seminars in Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Cytotoxic chemotherapy for acute myeloid leukemia (AML) usually produces only temporary remissions, at the cost of significant toxicity and risk for death. One fundamental reason for treatment failure is that it is designed to activate apoptosis genes (eg, TP53) that may be unavailable because of mutation or deletion. Unlike deletion of apoptosis genes, genes that mediate cell cycle exit by differentiation are present in myelodysplastic syndrome (MDS) and AML cells but are epigenetically repressed: MDS/AML cells express high levels of key lineage-specifying transcription factors. Mutations in these transcription factors (eg, CEBPA) or their cofactors (eg., RUNX1) affect transactivation function and produce epigenetic repression of late-differentiation genes that antagonize MYC. Importantly...

A critical appraisal of experimental intracerebral hemorrhage research

Journal of Cerebral Blood Flow — Wed, 01 Feb 2012 05:00:00 +0100

Authors: Crystal L MacLellan, Rosalie Paquette & Frederick Colbourne (Source: Journal of Cerebral Blood Flow)

Synergistic effects of CNS‐directed gene therapy and bone marrow transplantation in the murine model of infantile neuronal ceroid lipofuscinosis

Annals of Neurology — Wed, 01 Feb 2012 05:00:00 +0100

AbstractObjective:Infantile neuronal ceroid lipofusciniosis (INCL) is an inherited childhood neurodegenerative disorder caused by the loss of palmitoyl protein thioesterase‐1 (PPT1) activity. Affected children suffer from blindness, epilepsy, motor dysfunction, cognitive decline, and premature death. The Ppt1‐/‐ mouse shares the histological and clinical features of INCL. Previous single‐therapy approaches using small molecule drugs, gene therapy, or neuronal stem cells resulted in partial histological correction, with minimal improvements in motor function or lifespan. Here, we combined CNS‐directed AAV2/5‐mediated gene therapy with bone marrow transplantation (BMT) in the INCL mouse.Methods:At birth, Ppt1‐/‐ and WT mice were given either intracranial injections of AAV2/5�...

Xenogeneic and endogenous spermatogenesis following transplantation of rat germ cells into testes of immunocompetent mice.

Reproduction, Fertility, and Development — Wed, 01 Feb 2012 05:00:00 +0100

Authors: Qu N, Naito M, Li J, Terayama H, Hirai S, Itoh M Abstract Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis, and are characterised by their ability to self-renew and to produce differentiated progeny that form spermatozoa. It has been demonstrated that rat spermatogenesis can occur in the seminiferous tubules of congenitally immunodeficient recipient mice after transplantation of rat SSCs. However, the testis is often viewed as an immune-privileged site in that autoimmunogenic antigens on germ cells do not normally elicit an immune response in situ. In the present study, we tried to transplant rat SSCs into immunocompetent mice after depletion of their own germ cells by means of busulfan. The results showed that some transplanted SSCs could undergo com...

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Stem Cell Therapy Promising in Progressive MSStem Cell Therapy Promising in Progressive MS

Medscape Today Headlines — Tue, 31 Jan 2012 19:50:35 +0100

A small proof-of-concept study hints that autologous mesenchymal stem cells may have neuroprotective effects in patients with secondary progressive multiple sclerosis. Medscape Medical News (Source: Medscape Today Headlines)

Stem Cells May Further Hepatitis C Research

MedlinePlus Health News — Tue, 31 Jan 2012 19:00:00 +0100

Using liver-like cells, scientists hope to learn how some people resist infectionSource: HealthDay Related MedlinePlus Pages: Hepatitis C, Stem Cells (Source: MedlinePlus Health News)

Incidence, kinetics, and risk factors of Epstein–Barr virus viremia in pediatric patients after allogeneic stem cell transplantation

Pediatric Transplantation — Tue, 31 Jan 2012 18:43:29 +0100

Bordon V, Padalko E, Benoit Y, Dhooge C, Laureys G. Incidence, kinetics, and risk factors of Epstein–Barr virus viremia in pediatric patients after allogeneic stem cell transplantation.  Pediatr Transplantation 2012. © 2012 John Wiley & Sons A/S.Abstract: After allogeneic hematopoietic stem‐cell transplantation (allo‐HSCT), EBV infections can be potentially dangerous and even life threatening. We evaluated the EBV viremia in 80 consecutive allo‐HSCT with quantitative EBV‐PCR every 2 weeks during the first 3 months and monthly thereafter until 1 yr after allo‐HSCT or until death. We found a significantly more frequent viremia in patients who had in vivo T‐cell depletion in which 23 out of 51 (45%) had EBV‐PCR positivity. The EBV virus load was also significan...

Learn about the Political Highs and Lows for Science in 2011

Public Policy Reports — Tue, 31 Jan 2012 12:37:03 +0100

Now that 2011 is in the books, it is worth pausing briefly to consider some of the year’s notable science policy developments at the White House, in the Capitol, and across the nation. Among the highlights: Congress nearly shutdown the federal government in April by failing to reach a compromise on fiscal year 2011 spending. A last minute spending deal cut budgets for nearly all federal science programs. President Obama signed into law a reauthorization of the America COMPETES Act. Federal agencies developed policies to ensure scientific integrity. In July, a federal judge dismissed a case brought against the federal government that had previously halted federally funded research involving human embryonic stem cells. Dr. John C. Wingfield was named the new Assistant Director for N...

Become an Advocate for Science: Join the AIBS Legislative Action Center

Public Policy Reports — Tue, 31 Jan 2012 12:37:03 +0100

Quick, free, easy, effective, impactful! Join the AIBS Legislative Action Center today! The AIBS Legislative Action Center is an online resource that allows biologists and science educators to quickly and effectively influence policy and public opinion. Each day lawmakers must make tough decisions about science policy. For example, what investments to make in federal research programs, how to conserve biodiversity, how to mitigate climate change, or under what circumstances to permit stem cell research. Scientists now have the opportunity to help elected officials understand these issues. This exciting new advocacy tool allows individuals to quickly and easily communicate with members of Congress, executive branch officials, and selected media outlets. This new tool is made possible thro...

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Scientists Transform Skin Cells Direct To Brain Cells, Bypassing Stem Cell Stage

Health News from Medical News Today — Tue, 31 Jan 2012 10:00:00 +0100

Bypassing the stem cell stage, researchers at the Stanford University School of Medicine in California converted mouse skin cells directly into neural precursor cells, the cells that go on to form the three main types of cell in the brain and nervous system. They write about their findings in the 30 January early online issue of the Proceedings of the National Academy of Sciences... (Source: Health News from Medical News Today)

Cellular response of healing tissue to DegraPol tube implantation in rabbit Achilles tendon rupture repair: an in vivo histomorphometric study

Journal of Tissue Engineering and Regenerative Medicine — Tue, 31 Jan 2012 05:00:00 +0100

AbstractIn tendon rupture repair, improvements such as higher primary repair strength, anti‐adhesion and accelerated healing are needed. We developed a potential carrier system of an electrospun DegraPol® tube, which was tightly implanted around a transected and conventionally sutured rabbit Achilles tendon. Histomorphometric analysis of the tendon tissue 12 weeks postoperation showed that the tenocyte density, tenocyte morphology and number of inflammation zones were statistically equivalent, whether or not DegraPol tube was implanted; only the collagen fibres were slightly less parallelly orientated in the tube‐treated case. Comparison of rabbits that were operated on both hind legs with ones that were operated on only one hind leg showed that there were significantly more inflamm...

New cell-therapy technique may obviate stem-cell research

Physics Today News Picks — Tue, 31 Jan 2012 05:00:00 +0100

BBC: Researchers at Stanford University School of Medicine have succeeded in converting mouse skin cells into "neural precursor" cells, which can develop into three types of brain cell. The group's findings, which have been published in the Proceedings of the National Academy of Sciences, may be important for certain medical therapies, such as bone marrow transplants. Until now such transplants have relied on stem cells, which can divide and differentiate into many different specialized cell types. Stem-cell research has been hampered by ethical concerns, however, because one source of the cells has been human embryos. More work will have to be done to re-create the experiment using human skin cells. (Source: Physics Today News Picks)

Cancer Stem Cells: Distinct Entities or Dynamically Regulated Phenotypes?

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

The origins of tumor-propagating neoplastic stem-like cells [cancer stem cells (CSC)] and their relationship to the bulk population of tumor cells that lack stem-like tumor-propagating features (i.e., transit-amplifying cancer progenitor cells) remain unclear. Recent findings from multiple laboratories show that cancer progenitor cells have the capacity to dedifferentiate and acquire a stem-like phenotype in response to either genetic manipulation or environmental cues. These findings suggest that CSCs and relatively differentiated progenitors coexist in dynamic equilibrium and are subject to bidirectional conversion. In this review, we discuss emerging concepts regarding the stem-like phenotype, its acquisition by cancer progenitor cells, and the molecular mechanisms involved. Understandi...

Targeting Quiescent Tumor Cells via Oxygen and IGF-I Supplementation

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

In this study, we used a 3-dimensional tissue culture system to assay diffusible factors that can limit proliferation in the context of the tumor microenvironment, with the goal of identifying targets to heighten proliferative capacity in this setting. We found that supraphysiologic levels of insulin or insulin-like growth factor I (IGF-I) in combination with oxygen supplementation were sufficient to initiate proliferation of quiescence cells in this system. At maximal induction with IGF-I, net tissue proliferation increased 3- to 4-fold in the system such that chemotherapy could trigger a 3- to 6-fold increase in cytotoxicity, compared with control conditions. These effects were confirmed in vivo in colon cancer xenograft models with demonstrations that IGF-I receptor stimulation was suff...

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SMYD3 Promotes Cancer Invasion by Epigenetic Upregulation of the Metalloproteinase MMP-9

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

Upregulation of the matrix metalloproteinase (MMP)–9 plays a central role in tumor progression and metastasis by stimulating cell migration, tumor invasion, and angiogenesis. To gain insights into MMP-9 expression, we investigated its epigenetic control in a reversible model of cancer that is initiated by infection with intracellular Theileria parasites. Gene induction by parasite infection was associated with trimethylation of histone H3K4 (H3K4me3) at the MMP-9 promoter. Notably, we found that the H3K4 methyltransferase SMYD3 was the only histone methyltransferase upregulated upon infection. SMYD3 is overexpressed in many types of cancer cells, but its contributions to malignant pathophysiology are unclear. We found that overexpression of SMYD3 was sufficient to induce MMP-9 expression...

Long‐term effect of the self‐management comprehensive coping strategy program on quality of life in patients with breast cancer treated with high‐dose chemotherapy

Psycho-Oncology — Tue, 31 Jan 2012 05:00:00 +0100

ConclusionsThe CCSP improved QOL for patients at 1‐year follow‐up. Patients overwhelmingly reported that CCSP was beneficial. The CCSP as an effective coping intervention has potential as a self‐management program for breast cancer survivors. Copyright © 2012 John Wiley & Sons, Ltd. (Source: Psycho-Oncology)

Prevention of adverse cardiac remodeling to volume overload in female rats is the result of an estrogen-altered mast cell phenotype

AJP: Heart and Circulatory Physiology — Tue, 31 Jan 2012 05:00:00 +0100

The objective of this study was to determine the effect of female hormones on this initial cascade. Accordingly, an aortocaval fistula (Fist) was created in 7-wk-old Int and OVX rats, which, together with sham-operated (sham) controls, were studied at 1, 3, and 5 days postsurgery. In Int-Fist rats, myocardial mast cell density, collagen volume fraction, endothelin (ET)-1, stem cell factor (SCF), and TNF-α remained at control levels or were minimally elevated throughout the study period. This was not the case in the OVX-Fist group, where the initial response included significant increases in mast cell density, collagen degradation, ET-1, SCF, and TNF-α. These events in the OVX-Fist group were abolished by prefistula treatment with a mast cell stabilizer nedocromil. Of note was t...

Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma

British Journal of Pharmacology — Tue, 31 Jan 2012 05:00:00 +0100

SummaryThe incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up‐to‐date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum‐derivatives and pemetrexed or raltitrexed, as preferred first‐line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy‐...

Novel developmental biology‐based protocol of embryonic stem cell differentiation to morphologically sound and functional yet immature hepatocytes

Liver International — Tue, 31 Jan 2012 05:00:00 +0100

ConclusionWe report a novel protocol for hESC differentiation into morphological and functional yet immature hepatocytes as an alternative method for hepatocyte generation. (Source: Liver International)

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Characterization of Ocular Surface Epithelial and Progenitor Cell Markers in Human Adipose Stromal Cells Derived from Lipoaspirates [Cornea]

Investigative Ophthalmology — Tue, 31 Jan 2012 05:00:00 +0100

Conclusions. The expression of putative stem cell markers (CD90, ABCG2, and p63) and cytokeratins (CK12 and CK76) supports the hypothesis that ADS cells have self-renewal capacity and intrinsic plasticity that enables them to acquire some epithelial-like characteristics. Therefore, adult ADS cells could be a potential source for cell therapy in ocular surface regeneration. (Source: Investigative Ophthalmology)

Transforming growth factor‐β1 polymorphisms and the outcome of hematopoietic stem cell transplantation

International Journal of Immunogenetics — Mon, 30 Jan 2012 17:55:19 +0100

SummaryHematopoietic stem cell transplantation (HSCT) is a medical procedure used to treat malignant and nonmalignant haematological diseases, congenital immunodeficiency syndromes, solid tumours and metabolic diseases. Despite its usefulness, several major complications, such as graft‐versus‐host disease, can negatively affect patients treated with HSCT. Apart from clinical factors well known to affect the outcome of HSCT, patient and donor genetics have been shown to play an important role in the susceptibility to post‐transplant complications. Histocompatibility as determined by the human leucocyte antigen (HLA) system has been a major genetic determinant of the success of HSCT. Non‐HLA immunogenetics are increasingly recognized to play a part in the events related to transplant...

Need muscle for a tough spot? Turn to fat stem cells

ScienceDaily Headlines — Mon, 30 Jan 2012 14:43:43 +0100

Stem cells derived from fat have a surprising trick up their sleeves: Encouraged to develop on a stiff surface, they undergo a remarkable transformation toward becoming mature muscle cells. The new cells remain intact and fused together even when transferred to an extremely stiff, bone-like surface, which has bioengineers intrigued. These cells, they suggest, could hint at new therapeutic possibilities for muscular dystrophy. (Source: ScienceDaily Headlines)

Skin Cells as Stem Cells! Medicine's Next Big Thing

Medical Headlines From Ivanhoe.com — Mon, 30 Jan 2012 05:00:00 +0100

(Ivanhoe Newswire) -- Stem cells, they could hold the key to the treatment and cure of more than 70 major diseases and conditions. (Source: Medical Headlines From Ivanhoe.com)

FASEB SRC Announces Conference Registration Open for: Skeletal Muscle Satellite and Stem Cells

EurekAlert! - Biology — Mon, 30 Jan 2012 05:00:00 +0100

(Federation of American Societies for Experimental Biology) The Federation of American Societies for Experimental Biology announces the opening of registration for the Science Research Conference: Skeletal Muscle Satellite and Stem Cells. (Source: EurekAlert! - Biology)

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Effects of Wnt/β‐catenin signalling on proliferation and differentiation of apical papilla stem cells

Cell Proliferation — Mon, 30 Jan 2012 05:00:00 +0100

Conclusion: Our results suggest that canonical Wnt/β‐catenin signalling promotes proliferation and odonto/osteogenic differentiation of SCAP. (Source: Cell Proliferation)

Mesenchymal stem cells in the colorectal tumour microenvironment – recent progress and implications

International Journal of Cancer — Mon, 30 Jan 2012 05:00:00 +0100

AbstractMesenchymal stem cells (MSCs) are non haematopoietic multipotent adult stem cells. They have been shown to have a natural tropism for many tumours types, including colorectal, and are capable of escaping host immune surveillance. MSCs are known to engraft at tumours and integrate into their architecture, potentially as carcinoma associated fibroblasts (CAFs). In contrast with other malignancies, our understanding of the interactions between colorectal cancer cells and MSCs remains limited. Considering the established importance of inflammation in the colorectal cancer primary tumour microenvironment and the role of stromal cells in this process, there is a potential wealth of information to be gleaned from further investigation of interactions between these cell populations. Epithe...

Risk models predicting survival after reduced‐intensity transplantation for myelofibrosis

British Journal of Haematology — Sun, 29 Jan 2012 21:56:57 +0100

In conclusion, a simple model which includes: age, JAK2 V617F‐status and constitutional symptoms can clearly separate distinct risk groups and can be used in addition to the Lille model to predict OS after RIC‐ASCT for myelofibrosis. (Source: British Journal of Haematology)

Effect of scaffold dilution on migration of mesenchymal stem cells from fibrin hydrogels.

American Journal of Veterinary Research — Sun, 29 Jan 2012 12:42:27 +0100

Conclusions and Clinical Relevance-MSC migration from fibrin hydrogels increased with dilution of the fibrinogen component for both autologous and commercial sources. These data supported the feasibility of using diluted fibrin hydrogels for rapid delivery of MSCs to the surface of damaged tissues. PMID: 22280396 [PubMed - in process] (Source: American Journal of Veterinary Research)

Oxford, Harvard scientists lead data-sharing effort

EurekAlert! - Social and Behavioral Science — Sun, 29 Jan 2012 05:00:00 +0100

(Harvard University) Led by researchers at University of Oxford and the Harvard Stem Cell Institute at Harvard University, more than 50 collaborators at over 30 scientific organizations around the globe have agreed on a common standard that will make possible the consistent description of enormous and radically different databases compiled in fields ranging from genetics to stem cell science, to environmental studies. (Source: EurekAlert! - Social and Behavioral Science)

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A risk score for early cytomegalovirus reactivation after allogeneic stem cell transplantation identifies low‐, intermediate‐, and high‐risk groups: reactivation risk is increased by graft‐versus‐host disease only in the intermediate‐risk group

Transplant Infectious Disease — Sun, 29 Jan 2012 05:00:00 +0100

ConclusionsIdentification of these 3 risk groups in association with the presence or absence of GVHD will help transplant units to make pre‐transplant policy decisions about prophylactic, pre‐emptive, or experimental CMV prevention strategies in groups of patients undergoing HSCT, as well as in those developing GVHD post transplant. (Source: Transplant Infectious Disease)

Cloning scientists create human brain cells

Guardian Unlimited Science — Sun, 29 Jan 2012 00:07:00 +0100

Scientists in Edinburgh who pioneered cloning have made a technological breakthrough that could pave the way for better medical treatment of mental illnesses and nerve diseasesThe news that Edinburgh scientists had created the world's first cloned mammal, Dolly the sheep, at the university's Roslin Institute made headlines around the world 16 years ago. Her birth raised hopes of the creation of a new generation of medicines – with a host of these breakthroughs occurring at laboratories in the university over the following decade.And now one of the most spectacular has taken place at Edinburgh's Centre for Regenerative Medicine, where scientists have continued to develop the technology used to make Dolly. In a series of remarkable experiments, they have created brain tissue from patients ...

Telomere dysfunctional environment induces loss of quiescence and inherent impairments of hematopoietic stem cell function

Aging Cell — Sat, 28 Jan 2012 18:10:22 +0100

Previous studies have shown that telomere dysfunction induces alteration in the systemic (circulatory) environment impairing the differentiation of hematopoietic stem cells (HSCs) but these defects can be reverted by re‐exposing HSCs to an environment with functional telomeres. In contrast, HSC intrinsic telomere dysfunction induces permanent and irreversible limitations in the repopulation capacity partially depending on the induction checkpoints such as cell cycle arrest or apoptosis. It is currently unknown whether telomere dysfunctional environment can induce irreversible, cell intrinsic defects impairing the function of HSCs. Here we analyzed the functional reserves of murine, wildtype HSCs with intact telomeres that were transiently exposed to a telomere dysfunctional environment (...

Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

BMC Cancer — Sat, 28 Jan 2012 05:00:00 +0100

Conclusions: We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, SiHa, Ca Ski and C-4 I) and found that they express characteristic markers of stem cell, EMT and radioresistance. The fact that CICs demonstrated a higher degree of resistance to radiation than differentiated cells suggests that specific detection and targeting of CICs could be highly valuable for the therapy of tumors from the uterine cervix. (Source: BMC Cancer)

Hypoxic Preconditioning Enhances Survival of Human Adipose-Derived Stem Cells and Conditions Endothelial Cells In Vitro

Stem Cells and Development — Sat, 28 Jan 2012 04:16:59 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

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Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell–based therapy and case report on cell transplantation

Liver Transplantation — Sat, 28 Jan 2012 00:45:24 +0100

In conclusion, this human FL cell isolation protocol may be of interest for further clinical translation work on the development of liver cell–based therapies. Liver Transpl 18:226–237, 2012. © 2011 AASLD. (Source: Liver Transplantation)

A working life: the geneticist

Guardian Unlimited Science — Fri, 27 Jan 2012 23:02:30 +0100

Joe Rainger might still have been a chef, but for a degree change that took him out of the kitchen and plunged him into a world of DNA researchPeople born with abnormal eyes could – within our lifetime – benefit from replacements that match their own DNA, thanks to research by scientists like Joe Rainger.The 35-year-old geneticist is researching a mutation in human genes that causes microphthalmia (one or both eyes abnormally small), anophthalmia (absence of one or both eyes), and coloboma (a gap in the structure of the eye). The conditions are recessive; which means you need both parents to carry the defective gene for the conditions to appear. They are therefore most common in families where first cousins marry.Rainger, who works at the Medical Research Council's human genetics unit ...

Quantification of MSCs involved in wound healing: use of SIS to transfer MSCs to wound site and quantification of MSCs involved in skin wound healing

Journal of Tissue Engineering and Regenerative Medicine — Fri, 27 Jan 2012 21:43:21 +0100

This study traced MSCs participating in wound healing by using small intestinal submucosa (SIS) as a cell carrier, identified their moving path and calculated the number of MSCs involved in wound healing. First, MSCs were isolated from the nude mouse and 1 × 106 cells were seeded onto the centre of the SIS. MSC‐seeded SIS complexes were injected onto full‐thickness skin wounds made on the dorsum of nude mice. Tracing of MSC‐seeded SIS complex transplanted to the wound site revealed that 27.6% of the MSCs were migrated to the wound site at the first attempt. Second, repeated injection of additional MSCs did not increase the number of MSCs participating in wound healing beyond a certain constant maximum amount. The number of MSCs present in the wound site remains constant in the r...

Robust, quantitative tools for modelling ex-vivo expansion of haematopoietic stem cells and progenitors

RSC - Mol. BioSyst. latest articles — Fri, 27 Jan 2012 21:43:03 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05439F, PaperDavid A. Winkler, Frank R. BurdenModern computational modelling tools offer rapid, robust analysis of factors controlling expansion of haematopoietic stem cells and progenitors in bioreactors.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Balancing self‐renewal and differentiation by asymmetric division: Insights from brain tumor suppressors in Drosophila neural stem cells

BioEssays — Fri, 27 Jan 2012 21:40:09 +0100

AbstractBalancing self‐renewal and differentiation of stem cells is an important issue in stem cell and cancer biology. Recently, the Drosophila neuroblast (NB), neural stem cell has emerged as an excellent model for stem cell self‐renewal and tumorigenesis. It is of great interest to understand how defects in the asymmetric division of neural stem cells lead to tumor formation. Here, we review recent advances in asymmetric division and the self‐renewal control of Drosophila NBs. We summarize molecular mechanisms of asymmetric cell division and discuss how the defects in asymmetric division lead to tumor formation. Gain‐of‐function or loss‐of‐function of various proteins in the asymmetric machinery can drive NB overgrowth and tumor formation. These proteins control either the...

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Podcast: Magic Mushrooms, Sleeptalking Dolphins, and a Breakthrough for Embryonic Stem Cells

ScienceNOW — Fri, 27 Jan 2012 21:20:03 +0100

Listen to a roundup of some of our favorite stories from this week (Source: ScienceNOW)

Biomimetic composites and stem cells interaction for bone and cartilage tissue regeneration

RSC - J. Mater. Chem. latest articles — Fri, 27 Jan 2012 18:02:50 +0100

J. Mater. Chem., 2012, Advance ArticleDOI: 10.1039/C1JM14401D, Feature ArticleN. Naveena, J. Venugopal, R. Rajeswari, S. Sundarrajan, R. Sridhar, M. Shayanti, S. Narayanan, S. RamakrishnaThis review discusses the approaches that have been taken in bone and cartilage tissue engineering with an emphasis on the cell sources such as embryonic stem cells, adipose derived stem cells, mesenchymal stem cells and progenitor stem cells.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - J. Mater. Chem. latest articles)

Stem Cell Eye Therapy Shows Promise

NPR Health and Science — Fri, 27 Jan 2012 18:00:00 +0100

Reporting inThe Lancet, researchers write that a preliminary study shows embryonic stem cell therapy in two patients with macular degeneration was safe. Results suggest the patients' vision improved slightly. Dr. Robert Lanza, Chief Scientific Officer of Advanced Cell Technology and co-author of the study, discusses the trial.» E-Mail This » Add to Del.icio.us (Source: NPR Health and Science)

Fabrication and evaluation of biomimetic-synthetic nanofibrous composites for soft tissue regeneration

Cell and Tissue Research — Fri, 27 Jan 2012 17:54:30 +0100

Abstract Electrospun scaffolds hold promise for the regeneration of dense connective tissues, given their nanoscale topographies, provision of directional cues for infiltrating cells and versatile composition. Synthetic slow-degrading scaffolds provide long-term mechanical support and nanoscale instructional cues; however, these scaffolds suffer from a poor infiltration rate. Alternatively, nanofibrous constructs formed from natural biomimetic materials (such as collagen) rapidly infiltrate but provide little mechanical support. To take advantage of the positive features of these constructs, we have developed a composite scaffold consisting in both a biomimetic fiber fraction (i.e., Type I collagen nanofibers) together with a traditional synthetic (i.e., poly-[ε-caprolacto...

Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis

Cell and Tissue Research — Fri, 27 Jan 2012 17:54:29 +0100

Abstract Mesenchymal stem cells (MSCs) hold promise for cell-based therapy in regenerative medicine. To date, MSCs have been obtained from conventional bone marrow via a highly invasive procedure. Therefore, MSCs are now also isolated from sources such as adipose tissue, cord blood and cord stroma, a subject of growing interest. As the characterization and differentiation potential of adipose-derived MSCs (AD-MSCs) and bone-marrow-derived MSCs (BM-MSCs) have not been documented, we have evaluated and compared the characteristics of both MSC types by qualitative and quantitative analyses. Both cell types show similar morphology and surface protein expression, being positive for stromal-associated markers and negative for hematopoietic and endothelial markers. The colony-for...

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Stem cell-based tissue engineering in veterinary orthopaedics

Cell and Tissue Research — Fri, 27 Jan 2012 17:54:29 +0100

Abstract Regenerative medicine is one of the most intensively researched medical branches, with enormous progress every year. When it comes to translating research from bench to bedside, many of the pioneering innovations are achieved by cooperating teams of human and veterinary medical scientists. The veterinary profession has an important role to play in this new and evolving technology, holding a great scientific potential, because animals serve widely as models for human medicine and results obtained from animals may serve as preclinical results for human medicine. Regenerative veterinary medicine utilizing mesenchymal stromal cells (MSC) for the treatment of acute injuries as well as chronic disorders is gradually turning into clinical routine. As orthopaedic disorder...

The novel expression of Oct3/4 and Bmi1 in the root development of mouse molars

Cell and Tissue Research — Fri, 27 Jan 2012 17:54:29 +0100

This study aimed to investigate the characteristics of the cells involved in the root elongation. Octamer-binding factor 3/4 (Oct3/4) is known as one of the key regulators in maintaining the pluripotency and self-renewal properties of embryonic stem cells. Bmi1, the polycomb-group transcriptional repressor, has emerged as a key regulator in several cellular processes including stem cell self-renewal and cancer cell proliferation. At the beginning of root formation, ameloblasts expressed Oct3/4 in the nucleus, except in the apex of the cervical loop, in which Bmi1and cyclinD were expressed. At PN6, the expression of Oct3/4 in the ameloblasts shifted from the nucleus to the cytoplasm, whereas ameloblastin-negative Hertwig’s epithelial root sheath (HERS) cells expressed Bmi1 and cycli...

Antineoplastic agent busulfan regulates a network of genes related to coagulation and fibrinolysis

European Journal of Clinical Pharmacology — Fri, 27 Jan 2012 17:52:03 +0100

Conclusions This is the first report that directly relates busulfan exposure to antifibrinolytic activity by PAI-1 and hypercoagulation possibly mediated by members of the TGF-β1 family. This suggests further research to evaluate activin A and TGF-β1 as potential targets for HVOD treatment. Content Type Journal ArticleCategory PharmacodynamicsPages 1-13DOI 10.1007/s00228-011-1209-yAuthors Janka Reimer, Research Center of Pharmacology and Experimental Therapeutics, Department of Pharmacology, Ernst-Moritz-Arndt-University of Greifswald, Greifswald, GermanySandra Bien, Research Center of Pharmacology and Experimental Therapeutics, Department of Pharmacology, Ernst-Moritz-Arndt-University of Greifswald, Greifswald, GermanySabine Ameling, Department of Functional Geno...

Findings

Science: Current Issue — Fri, 27 Jan 2012 17:42:31 +0100

Signature of Senescence | Embryonic Stem Cells for Eye Disease Appear Safe (Source: Science: Current Issue)

Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients

International Journal of Clinical Practice — Fri, 27 Jan 2012 14:21:21 +0100

Conclusion: The transplantation of BMCs as well as TRCs proved to be safe and feasible. Improvements of microcirculation and complete wound healing were observed in the transplant groups. (Source: International Journal of Clinical Practice)

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Successful isolation of liver progenitor cells by aldehyde dehydrogenase activity in naïve mice

Hepatology — Fri, 27 Jan 2012 14:20:30 +0100

Conclusion: High ALDH activity is a feature of LPCs that can be taken advantage of to isolate these cells from untreated mouse as well as human liver tissues. This novel protocol is practically relevant, because it provides an easy and nontoxic method to isolate liver stem cells from normal tissue for potential therapeutic purposes. (HEPATOLOGY 2012) (Source: Hepatology)

A First For Ontario: Cardiac Stem Cell Transplant Performed At The Peter Munk Cardiac Centre

Health News from Medical News Today — Fri, 27 Jan 2012 10:00:00 +0100

Heart failure is a leading cause of death in Canada. As part of the ongoing IMPACT-CABG clinical trial to treat advanced heart failure, physicians at the Peter Munk Cardiac Centre performed the first cardiac stem cell transplant in Ontario last week using stem cells derived from the patient's own bone marrow, isolated completely within the operating room, and implanted into the heart at the time of coronary bypass surgery. Researchers hope that stem cell therapy may be developed into a novel treatment for the 50,000 Canadians diagnosed each year with advanced heart failure... (Source: Health News from Medical News Today)

A Path To The Brain Through The Nose Aids Schizophrenia Research

Health News from Medical News Today — Fri, 27 Jan 2012 08:00:00 +0100

A significant obstacle to progress in understanding psychiatric disorders is the difficulty in obtaining living brain tissue for study so that disease processes can be studied directly. Recent advances in basic cellular neuroscience now suggest that, for some purposes, cultured neural stem cells may be studied in order to research psychiatric disease mechanisms. But where can one obtain these cells outside of the brain? Increasingly, schizophrenia research is turning to the nose... (Source: Health News from Medical News Today)

3D Biomatrix™ to Exhibit Perfecta3D™ Hanging Drop Plates at Stem Cells...

PRWeb: Medical Pharmaceuticals — Fri, 27 Jan 2012 06:33:34 +0100

3D Biomatrix, which develops and markets three-dimensional cell culture products, will be exhibiting its Perfecta3DTM Hanging Drop Plates at the Stem Cells 2012 and Cell Culture 2012 shows in San...(PRWeb January 25, 2012)Read the full story at http://www.prweb.com/releases/2012/1/prweb9132242.htm (Source: PRWeb: Medical Pharmaceuticals)

Stemedica Completes Pre-IND Meeting with the FDA for Ischemic Tolerant...

PRWeb: Medical Pharmaceuticals — Fri, 27 Jan 2012 06:33:34 +0100

Stemedica announced that it completed its pre-IND meeting with the U.S. Food and Drug Administration (FDA) regarding a proposed IND (Investigational New Drug) application to evaluate the safety and...(PRWeb January 24, 2012)Read the full story at http://www.prweb.com/releases/2012-stemedica-FDA/PRE-IND-ITNSC-STEM-CELL/prweb9133781.htm (Source: PRWeb: Medical Pharmaceuticals)

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Acute leukemias of ambiguous lineage

Seminars in Diagnostic Pathology — Fri, 27 Jan 2012 05:38:40 +0100

The 2008 edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues recognizes a special category called “leukemias of ambiguous lineage.” The vast majority of these rare leukemias are classified as mixed phenotype acute leukemia (MPAL), although acute undifferentiated leukemias and natural killer lymphoblastic leukemias are also included. The major immunophenotypic markers used by the WHO 2008 to determine the lineage for these proliferations are myeloperoxidase, CD19, and cytoplasmic CD3. However, extensive immunophenotyping is necessary to confirm that the cells indeed belong to 2 different lineages or coexpress differentiation antigens of more than 1 lineage. Specific subsets of MPAL are defined by chromosomal anomalies such as the t(9;22) Philadelphia chrom...

A simple immunohistochemical algorithm predicts the risk of distant metastases in right‐sided colon cancer

Histopathology — Fri, 27 Jan 2012 05:24:10 +0100

Conclusions: By the use of three markers, this algorithm allowed identification of subgroups of right‐sided CC patients with extremely high and extremely low risk of distant metastases. (Source: Histopathology)

In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells

BMC Developmental Biology - Latest articles — Fri, 27 Jan 2012 05:00:00 +0100

Conclusions: Our data is the first to demonstrate that human dermal skin stromal cells can be differentiated into endothelial lineage. Hence, SSCs represents a novel source of stem/stromal cells for tissue regeneration and the vascularization of engineered tissues. Moreover, the CD146 investigations suggested that the microenvironmental niche might contribute to direct stromal cells multipotency toward certain lineages, which warrants further investigation. (Source: BMC Developmental Biology - Latest articles)

TGFß1 inhibits lymphatic endothelial cell differentiation from mouse embryonic stem cells

Journal of Cellular Physiology — Fri, 27 Jan 2012 05:00:00 +0100

AbstractThe lymphatic vasculature is essential for the maintenance of tissue fluid, immune surveillance and dissemination of metastasis. Recently, several models for lymphatic vascular research and markers specific for lymphatic endothelium have been characterized. Despite these significant achievements, our understanding of the early lymphatic development is still rather limited. The purpose of the study was to further define early lymphatic differentiation regulatory pathways. In the present study, we have developed conditions leading to lymphatic endothelial cell differentiation under both serum‐rich and serum‐free conditions, using the coculture system of Flk‐1‐positive vascular precursors derived from murine embryonic stem (ES) cells grown on an OP9 stromal cell layer. In this...

Targeting the enhancer of zeste homologue 2 in medulloblastoma

International Journal of Cancer — Fri, 27 Jan 2012 05:00:00 +0100

AbstractEnhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 that catalyzes the trimethylation of histone H3 on Lys 27, and represses gene transcription. EZH2 enhances cancer‐cell proliferation and regulates stem cell maintenance and differentiation. Here, we demonstrate that EZH2 is highly expressed in medulloblastoma, a highly malignant brain tumor of childhood, and this altered expression is correlated with genomic gain of chromosome 7 in a subset of medulloblastoma. Inhibition of EZH2 by RNAi suppresses medulloblastoma tumor cell growth. We show that 3‐deazaneplanocin A, a chemical inhibitor of EZH2, can suppress medulloblastoma cell growth partially by inducing apoptosis. Suppression of EZH2 expression diminishes the ability of tumor cells...

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Hair follicle stem cell differentiation is inhibited through a cross talk between Wnt/β‐catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia

British Journal of Dermatology — Fri, 27 Jan 2012 05:00:00 +0100

Conclusions: These results suggest that androgens deregulate DPC‐secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway. (Source: British Journal of Dermatology)

Can Adult Neural Stem Cells Create New Brains? Plasticity in the Adult Mammalian Neurogenic Niches: Realities and Expectations in the Era of Regenerative Biology

The Neuroscientist — Fri, 27 Jan 2012 05:00:00 +0100

Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balanc...

Need muscle for a tough spot? Turn to fat stem cells, UC San Diego researchers say

EurekAlert! - Medicine and Health — Fri, 27 Jan 2012 05:00:00 +0100

(University of California - San Diego) Stem cells derived from fat have a surprising trick up their sleeves: Encouraged to develop on a stiff surface, they undergo a remarkable transformation toward becoming mature muscle cells. The new cells remain intact and fused together even when transferred to an extremely stiff, bone-like surface, which has University of California, San Diego bioengineering professor Adam Engler and colleagues intrigued. These cells, they suggest, could hint at new therapeutic possibilities for muscular dystrophy. (Source: EurekAlert! - Medicine and Health)

Uremia induces functional incompetence of bone marrow-derived stromal cells

Nephrology Dialysis Transplantation — Fri, 27 Jan 2012 05:00:00 +0100

Conclusion. These results clearly demonstrate the functional incompetence in MSCs under uremic conditions and may significantly contribute to the disproportionately high risk for CVD in patients with CKD. (Source: Nephrology Dialysis Transplantation)

Scale‐up of MSC under hypoxic conditions for allogeneic transplantation and enhancing bony regeneration in a rabbit calvarial defect model

Journal of Orthopaedic Research — Fri, 27 Jan 2012 04:49:31 +0100

In conclusion, we have developed a robust method for isolation and expansion of rabbit MSCs by combining low‐density with hypoxic culture, which can be applied for the design of clinical trials in allogeneic transplantation of MSCs for bone healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res (Source: Journal of Orthopaedic Research)

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Lineage Selection-Neural Stem Cells for SC Grafts

Neuromics — Fri, 27 Jan 2012 00:21:00 +0100

In this study we investigate the effects of controlled Ngn1 expression on mouse ES (mES) cell differentiation in vitro and following grafting into the rat spinal cord. In vitro, Ngn1 expression in mES cells leads to rapid and specific neural differentiation, and a concurrent decrease in proliferation. Similarly transplantation of Ngn1-expressing mES cells into the spinal cord lead to in situ differentiation and spinal precursor formation. These data demonstrate that Ngn1 expression in mES cells is sufficient promote neural differentiation and inhibit proliferation, thus establishing an approach to safely graft ES cells into the spinal cord. Image: Neural progenitors were labeled with anti-rat Nestin polyclonal antibody (Cat#:GT15114) and stained with conjugated donkey anti-goat secondary a...

Regulation of KLF4 Turnover Reveals an Unexpected Tissue-Specific Role of pVHL in Tumorigenesis

Molecular Cell — Fri, 27 Jan 2012 00:00:00 +0100

Armin M. Gamper, Xinxian Qiao, Jennifer Kim, Liyong Zhang, Michelle C. DeSimone, W. Kimryn Rathmell, Yong Wan. The transcription factor Krüppel-like factor 4 (KLF4) is an important regulator of cell-fate decision, including cell-cycle regulation, apoptosis, and stem cell renewal, and plays an ambivalent ro.... (Source: Molecular Cell)

Lab Paradox May Explain Avastin's Effects (CME/CE)

MedPage Today Hematology/Oncology — Thu, 26 Jan 2012 21:13:07 +0100

(MedPage Today) -- Some anti-cancer agents may aid the growth of cancer stem cells -- paradoxically through the same mechanism they use to slow tumor growth, researchers reported. (Source: MedPage Today Hematology/Oncology)

Charter Medical Receives CE Mark Clearance for Next Generation Cell Freeze(R) Cryogenic Stem Cell Storage Containers

Medical News (via PRIMEZONE) — Thu, 26 Jan 2012 21:05:00 +0100

MANCHESTER, Conn., Jan. 26, 2012 (GLOBE NEWSWIRE) -- Charter Medical, Ltd., a Lydall subsidiary, (NYSE:LDL) announced today that it received CE Mark approval on its next generation Cell Freeze(r) Cryogenic Storage Containers for Hematopoietic Progenitor Cells (HPC's). The issuance of the approval by European regulators allows Charter Medical to begin marketing and selling the newly designed and expanded product offering for cryogenic storage, preservation, and transfer of HPC's in Europe. These next generation storage containers offer a broad size range from 50 mL to 750 mL and have excellent durability when frozen at ultralow (-196*C) temperatures. (Source: Medical News (via PRIMEZONE))

Br‐DIF‐1 accelerates dimethyl sulphoxide‐induced differentiation of P19CL6 embryonic carcinoma cells into cardiomyocytes

British Journal of Pharmacology — Thu, 26 Jan 2012 18:51:19 +0100

CONCLUSIONS AND IMPLICATIONS Br‐DIF‐1 accelerated the differentiation, induced by 1% DMSO, of P19CL6 cells into spontaneously beating cardiomyocyte‐like cells, partly by enhancing the expression of the T‐type Ca2+ channel gene. (Source: British Journal of Pharmacology)

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Autofluorescence in BrdU-Positive Cells and Augmentation of Regeneration Kinetics by Riboflavin

Stem Cells and Development — Thu, 26 Jan 2012 17:25:20 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Isolation of Novel Multipotent Neural Crest-Derived Stem Cells from Adult Human Inferior Turbinate

Stem Cells and Development — Thu, 26 Jan 2012 17:25:07 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Laminin-111 Stimulates Proliferation of Mouse Embryonic Stem Cells Through a Reduction of Gap Junctional Intercellular Communication via RhoA-Mediated Cx43 Phosphorylation and Dissociation of Cx43/ZO-1/Drebrin Complex

Stem Cells and Development — Thu, 26 Jan 2012 17:24:51 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Adipose-Derived Stem Cells Produce Factors Enhancing Peripheral Nerve Regeneration: Influence of Age and Anatomic Site of Origin

Stem Cells and Development — Thu, 26 Jan 2012 17:06:36 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Tip110 Maintains Expression of Pluripotent Factors in and Pluripotency of Human Embryonic Stem Cells

Stem Cells and Development — Thu, 26 Jan 2012 17:01:22 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

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Helios Transcription Factor Expression Depends on Gsx2 and Dlx1&2 Function in Developing Striatal Matrix Neurons

Stem Cells and Development — Thu, 26 Jan 2012 17:01:15 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Changes in Expression of the Antioxidant Enzyme SOD3 Occur Upon Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells In Vitro

Stem Cells and Development — Thu, 26 Jan 2012 17:01:04 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Stromal-Derived Factor-1 and Its Receptor, CXCR4, Are Constitutively Expressed by Mouse Liver Sinusoidal Endothelial Cells: Implications for the Regulation of Hematopoietic Cell Migration to the Liver During Extramedullary Hematopoiesis

Stem Cells and Development — Thu, 26 Jan 2012 16:56:37 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Synergistic Effect of Medium, Matrix, and Exogenous Factors on the Adhesion and Growth of Human Pluripotent Stem Cells Under Defined, Xeno-Free Conditions

Stem Cells and Development — Thu, 26 Jan 2012 16:54:20 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Human Fetal Oligodendrocyte Progenitor Cells from Different Gestational Stages Exhibit Substantially Different Potential to Myelinate

Stem Cells and Development — Thu, 26 Jan 2012 16:54:15 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

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Epithelial Cell Rests of Malassez Contain Unique Stem Cell Populations Capable of Undergoing Epithelial–Mesenchymal Transition

Stem Cells and Development — Thu, 26 Jan 2012 16:51:00 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

β-PIX Is Critical for Transplanted Mesenchymal Stromal Cell Migration

Stem Cells and Development — Thu, 26 Jan 2012 16:48:33 +0100

Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)

Syngeneic Hematopoietic Stem Cell Transplantation Enhances the Antitumor Immunity of Intratumoral Type I Interferon Gene Transfer for Sarcoma

Human Gene Therapy — Thu, 26 Jan 2012 16:31:59 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

First Experience in Humans Using Adipose Tissue–Derived Regenerative Cells in the Treatment of Patients With ST-Segment Elevation Myocardial Infarction

Journal of the American College of Cardiology — Thu, 26 Jan 2012 13:57:11 +0100

In preclinical animal models of acute myocardial infarction (AMI), administration of freshly isolated adipose tissue–derived regenerative cells (ADRCs) immediately after the AMI improved left ventricular (LV) function and myocardial perfusion (). The predominant working mechanism of ADRC therapy in AMI is believed to be through paracrine release of antiapoptotic, immunomodulatory, and proangiogenic factors. These factors evoke cardiomyocyte salvage and stimulate neoangiogenesis in the infarct border zone and eventually result in reduced infarct scar formation and adverse cardiac remodeling (). ADRCs comprise, among other cells, immune-competent cells, endothelial progenitor cells, and mesenchymal stem cells. The amount of these mesenchymal stem cells in freshly isolated adipose tissue di...

Overexpression of GDF5 through an Adenovirus Vector Stimulates Osteogenesis of Human Mesenchymal Stem Cells in vitro and in vivo

Karger Publishers — Thu, 26 Jan 2012 12:50:45 +0100

Cells Tissues Organs (DOI:10.1159/000330791) (Source: Karger Publishers)

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Breast Cancer Survival - Why Avastin And Sutent Don't Help

Health News from Medical News Today — Thu, 26 Jan 2012 12:00:00 +0100

Avastin and Sutent, two breast cancer drugs, do not lead to longer survival, probably because they encourage an increase in the number cancer stem cells in breast tumors, according to a study carried out on mice by researchers from the Michigan Comprehensive Cancer Center, and published in the Proceedings of the National Academy of Sciences (early edition). Even though Sutent (sunitinib) and Avastin (bevacizumab) do shrink breast cancer tumors and slow down the rate at which the cancer develops, their effects are short-lived - the cancers starts growing again and metastasizes (spreads)... (Source: Health News from Medical News Today)

Alzheimer's Neurons Induced From Pluripotent Stem Cells

Health News from Medical News Today — Thu, 26 Jan 2012 11:00:00 +0100

Led by researchers at the University of California, San Diego School of Medicine, scientists have, for the first time, created stem cell-derived, in vitro models of sporadic and hereditary Alzheimer's disease (AD), using induced pluripotent stem cells from patients with the much-dreaded neurodegenerative disorder... (Source: Health News from Medical News Today)

Blood-Forming Stem Cells' Growth Identified

Health News from Medical News Today — Thu, 26 Jan 2012 09:00:00 +0100

Scientists with the new Children's Research Institute at UT Southwestern Medical Center have identified the environment in which blood-forming stem cells survive and thrive within the body, an important step toward increasing the safety and effectiveness of bone-marrow transplantation. Institute investigators led by Dr. Sean Morrison asked which cells are responsible for the microenvironment that nurtures haematopoietic stem cells, which produce billions of new blood cells every day. The answer: endothelial and perivascular cells, which line blood vessels... (Source: Health News from Medical News Today)

Allogeneic stem cell transplantation versus conventional therapy for advanced primary cutaneous T-cell lymphoma.

Cochrane Database of Systematic Reviews — Thu, 26 Jan 2012 08:18:08 +0100

CONCLUSIONS: We planned to report evidence from genetically or non-genetically randomised controlled trials comparing conventional therapy and allogeneic stem cell transplantation. However, no randomised trials addressing this question were identified. Nevertheless, prospective genetically randomised controlled trials need to be initiated to evaluate the precise role of alloSCT in advanced CTCL. PMID: 22258991 [PubMed - in process] (Source: Cochrane Database of Systematic Reviews)

High-dose therapy with autologous stem cell transplantation versus chemotherapy or immuno-chemotherapy for follicular lymphoma in adults.

Cochrane Database of Systematic Reviews — Thu, 26 Jan 2012 08:18:08 +0100

CONCLUSIONS: In summary, the currently available evidence suggests a strong PFS benefit for HDT + ASCT compared with chemotherapy or immuno-chemotherapy in previously untreated patients with FL. No statistically significant differences in terms of OS, TRM and secondary cancers were detected. These effects are confirmed in a subgroup analysis (one trial) adding rituximab to both treatment arms. Further trials evaluating this approach are needed to determine this effect more precisely in the era of rituximab. Moreover, longer follow-up data are necessary to find out whether the PFS advantage will translate into an OS advantage in previously untreated patients with FL.There is evidence that HDT + ASCT is advantageous in patients with relapsed FL. PMID: 22258971 [PubMed - in process] (Sour...

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Data For Adipose Stem Cell Heart Attack Trial Published In JACC

Health News from Medical News Today — Thu, 26 Jan 2012 08:00:00 +0100

Cytori Therapeutics (NASDAQ: CYTX) has announced the publication of previously reported six-month outcomes from APOLLO, the Company's European clinical trial evaluating adipose-derived stem and regenerative cells (ADRCs) in patients with acute myocardial infarction (heart attack or AMI), as Research Correspondence in the Journal of the American College of Cardiology... (Source: Health News from Medical News Today)

Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer

BMC Cancer — Thu, 26 Jan 2012 05:00:00 +0100

Conclusion: ALDH1 expression and its prognostic effect are age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research. (Source: BMC Cancer)

Ontario's first cardiac stem cell transplant performed last week at the Peter Munk Cardiac Centre

EurekAlert! - Medicine and Health — Thu, 26 Jan 2012 05:00:00 +0100

(University Health Network) Peter Munk Cardiac Centre physicians performed the first cardiac stem cell transplant in Ontario, part of the IMPACT-CABG clinical trial, to treat advanced heart failure, using stem cells derived from the patient's bone marrow, isolated within the operating room, and implanted into the heart at the time of coronary bypass surgery. Researchers hope that stem cell therapy may be developed into a novel treatment for the 50,000 Canadians diagnosed each year with advanced heart failure. (Source: EurekAlert! - Medicine and Health)

Transplantation of human embryonic stem cells onto a partially wounded human cornea in vitro

Acta Ophthalmologica — Thu, 26 Jan 2012 05:00:00 +0100

Conclusion: This shows that it is possible to transplant cells originating from hESCs onto Bowman’s membrane with the epithelial layer partially removed and to get these cells to establish, grow and differentiate into corneal epithelial‐like cells in vitro. (Source: Acta Ophthalmologica)

The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia

Blood — Thu, 26 Jan 2012 05:00:00 +0100

An important mediator of cytokine signaling implicated in regulation of hematopoiesis is the PI3K/protein kinase B (PKB/c-Akt) signaling module. Constitutive activation of this signaling module has been observed in a large group of leukemias. Because activation of this signaling pathway has been demonstrated to be sufficient to induce hematologic malignancies and is thought to correlate with poor prognosis and enhanced drug resistance, it is considered to be a promising target for therapy. A high number of pharmacologic inhibitors directed against either individual or multiple components of this pathway have already been developed to improve therapy. In this review, the safety and efficacy of both single and dual-specificity inhibitors will be discussed as well as the potential of combinat...

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Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p

Blood — Thu, 26 Jan 2012 05:00:00 +0100

In conclusion, the adverse impact of del(17p13) on PFS and OS could be significantly reduced by bortezomib-based treatment, suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13). This trial is registered at the International Standard Randomised Controlled Trial Number Register as ISRCTN64455289. (Source: Blood)

TLR3 essentially promotes protective class I-restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients

Blood — Thu, 26 Jan 2012 05:00:00 +0100

Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8+ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8+ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4+ and CD8+ T cells mediate protective memory responses to the fungus contingent on the nature of the fungal vaccine. Mechanistically, class I MHC-restricted, CD8+ memory T cells were activated through TLR3 sensing of fungal RNA by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated with susceptibility to aspergillosis and concomitant failure to activate memory-protectiv...

Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the growth of hematopoietic cells expressing oncogenic Nras

Blood — Thu, 26 Jan 2012 05:00:00 +0100

The palmitoylation/depalmitoylation cycle of posttranslational processing is a potential therapeutic target for selectively inhibiting the growth of hematologic cancers with somatic NRAS mutations. To investigate this question at the single-cell level, we constructed murine stem cell virus vectors and assayed the growth of myeloid progenitors. Whereas cells expressing oncogenic N-RasG12D formed cytokine-independent colonies and were hypersensitive to GM-CSF, mutations within the N-Ras hypervariable region induced N-Ras mislocalization and attenuated aberrant progenitor growth. Exposing transduced hematopoietic cells and bone marrow from Nras and Kras mutant mice to the acyl protein thioesterase inhibitor palmostatin B had similar effects on protein localization and colony growth. Important...

IFN-{gamma} and indoleamine 2,3-dioxygenase signaling between donor dendritic cells and T cells regulates graft versus host and graft versus leukemia activity

Blood — Thu, 26 Jan 2012 05:00:00 +0100

Allogeneic hematopoietic stem cell transplantation (HSCT) can eradicate chemorefractory leukemia through the graft-versus-leukemia (GVL) activity of donor T cells. However, the clinical success of allo-HSCT is limited by the graft-versus-host disease (GVHD) activity of donor T cells. We have reported previously that donor bone marrow precursors of plasmacytoid dendritic cells (pre-pDCs) can activate donor T cells toward T-helper 1 immune polarization in murine allogeneic HSCT. To optimize the GVL activity of these activated donor T cells and limit their graft versus host activity, we engineered the cellular constituents of an allogeneic hematopoietic stem cell graft with highly purified hematopoietic stem cells, T cells, and pre-pDCs and studied their GVL and GVHD activities in a murine mo...

Hemopoietic stem cell transplantation failure followed by switch to stable production of fetal hemoglobin

Blood — Thu, 26 Jan 2012 05:00:00 +0100

(Source: Blood)

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Irradiated stem cells and ageing of the haematopoietic system.

Radiation and Environmental Biophysics — Thu, 26 Jan 2012 05:00:00 +0100

Authors: Vávrová J, Sinkorová Z, Rezáčová M, Tichý A, Filip S, Mokrý J, Lukášová E Abstract In the work presented here, changes in haematopoiesis of mice (B6129SF2/J) were studied 1 year after their whole-body exposure to a dose of 7 Gy (72% of mice survived). The irradiated mice were compared with non-irradiated younger (4 months of age) and older (16 months of age) mice. There was a significant increase in the relative abundance of primitive stem cells with long-term capability of the haematopoiesis recovery lin(-)/Sca-1(+)/CD117(+)/CD34(-) in the bone marrow of mice aged 16 months (irradiated and non-irradiated) compared with those aged 4 months. In terms of the ability to respond to further whole-body irradiation at a dose of 1 Gy, the presence of γH2A.X foci...

EGFR regulation of colon cancer stem-like cells during aging and in response to the colonic carcinogen dimethylhydrazine.

American Journal of Physiology. Gastrointestinal and Liver Physiology — Thu, 26 Jan 2012 05:00:00 +0100

Authors: Nautiyal J, Du J, Yu Y, Kanwar SS, Levi E, Majumdar AP Abstract One of the most consistent pathological conditions in the gastrointestinal (GI) tract with advancing age is malignancy, particularly GI cancers, the incidence of which increases sharply with aging. Although the reasons for the age-related rise in colorectal cancer are not fully understood, we hypothesize that aging increases susceptibility of the colon to carcinogen(s)/toxicant(s) leading to an increase in cancer stem-like cells (CSLCs) that express cancer stem cell markers, in the colonic mucosa. The current study demonstrates that aging is associated with increased expression of several colon CSLC markers: CD44, CD166 and ALDH-1 and a higher proportion of cells expressing these markers. Aging is also accompa...

Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone with or Without Radiotherapy in Primary Mediastinal Large B-Cell Lymphoma: The Emerging Standard of Care.

The Oncologist — Thu, 26 Jan 2012 05:00:00 +0100

Conclusions. Based on these results, most patients with PMLBCL appear to be cured by R-CHOP in 21-day cycles with or without RT, which could be the current standard of care. Therefore, the need for more aggressive treatment strategies is questionable unless high-risk patients are adequately defined. Further studies are required to establish the precise role of RT. PMID: 22282906 [PubMed - as supplied by publisher] (Source: The Oncologist)

Phase II Study of Gonadotropin-Releasing Hormone Analog for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients.

The Oncologist — Thu, 26 Jan 2012 05:00:00 +0100

Conclusion. Leuprolide did not preserve ovarian function in patients who underwent HSCT using either myeloablative or nonmyeloablative regimens. Other measures that protect ovarian function need to be investigated. PMID: 22282904 [PubMed - as supplied by publisher] (Source: The Oncologist)

Embryonic stem cells: can we make the blind see?

Forbes.com Healthcare News — Wed, 25 Jan 2012 21:06:56 +0100

In a new study, partial vision is restored to 2 patients with "irreversible" macular damage. Embryonic stem cells were used to repair the damage cells. (Source: Forbes.com Healthcare News)

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Heterogeneity and Randomness of DNA Methylation Patterns in Human Embryonic Stem Cells

DNA and Cell Biology — Wed, 25 Jan 2012 20:50:52 +0100

DNA and Cell Biology , Vol. 0, No. 0. (Source: DNA and Cell Biology)

Environmental parameters influence non-viral transfection of human mesenchymal stem cells for tissue engineering applications

Cell and Tissue Research — Wed, 25 Jan 2012 18:12:35 +0100

Abstract Non-viral transfection is a promising technique that could be used to increase the therapeutic potential of stem cells. The purpose of this study was to explore practical culture parameters of relevance in potential human mesenchymal stem cell (hMSC) clinical and tissue engineering applications, including type of polycationic transfection reagent, N/P ratio and dose of polycation/pDNA polyplexes, cell passage number, cell density and cell proliferation. The non-viral transfection efficiency was significantly influenced by N/P ratio, polyplex dose, cell density and cell passage number. hMSC culture conditions that inhibited cell division also decreased transfection efficiency, suggesting that strategies to promote hMSC proliferation may be useful to enhance transfe...

Approach to Assessing Myocardial Perfusion in Rats Using Static [13N]-Ammonia Images and a Small-Animal PET

Molecular Imaging and Biology — Wed, 25 Jan 2012 18:07:46 +0100

Conclusions The straightforward procedure described here (similar to those commonly used in clinical routine) was sufficient to yield statistically significant perfusion differences between the treated and untreated animals despite the small sample size. Content Type Journal ArticleCategory Brief ArticlePages 1-5DOI 10.1007/s11307-011-0538-7Authors Juan José Vaquero, Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Avda. de la Universidad 30, 28911 Leganés, Madrid, SpainDong-Wei Gao, Center for Molecular and Functional Imaging, University of California San Francisco, 185 Berry Street, Suite 350, 94107 San Francisco, CA, USACarmen García-Villaba, Unidad de Medicina y Cirugía Experimental, Hospital General Universitario G...

Management of Myeloproliferative Neoplasms: From Academic Guidelines to Clinical Practice

Current Hematologic Malignancy Reports — Wed, 25 Jan 2012 18:05:35 +0100

Abstract Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by excessive production of mature cells. In most of the classic Philadelphia-negative MPNs—polycythemia vera (PV), essential thrombocythemia (ET), and MPN-associated myelofibrosis (MPN-MF)—oncogenic mutations affecting JAK2 or MPL lead to constitutive activation of cytokine-regulated intracellular signalling pathways. The traditional therapy for PV and ET is the prevention of thrombotic events with antiproliferative agents in association with aspirin. New drugs such as pegylated interferon and anti-JAK agents are candidates for slowing the evolution to myelofibrosis or leukemia. Conventional therapy for MPN-MF is driven by clinical needs, primarily anemia and splenomegaly. Lenalidomide and ...

Blood-forming stem cells' growth identified in first breakthrough from new institute

UT Southwestern Medical Center News — Wed, 25 Jan 2012 18:00:00 +0100

Scientists with the new Children’s Research Institute at UT Southwestern have identified the environment in which blood-forming stem cells survive and thrive within the body. (Source: UT Southwestern Medical Center News)

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Blindness eased by historic stem cell treatment

New Scientist - Health — Wed, 25 Jan 2012 12:21:42 +0100

People with eye degeneration report better vision after controversial treatment based on human embryonic stem cells (Source: New Scientist - Health)

First Step In Strategy For Cell Replacement Therapy In Parkinson's Disease

Health News from Medical News Today — Wed, 25 Jan 2012 10:00:00 +0100

Induced pluripotent stem cells (iPSC) are a promising avenue for cell replacement therapy in neurologic diseases. For example, mouse and human iPSCs have been used to generate dopaminergic (DA) neurons that improve symptoms in rat Parkinson's disease models. Reporting in the current issue of the Journal of Parkinson's Disease, a group of scientists from Japan evaluated the growth, differentiation, and function of human-derived iPSC-derived neural progenitor cells (NPCs) in a primate model, elucidating their therapeutic potential... (Source: Health News from Medical News Today)

Therapeutically Useful Stem Cell Derivatives In Need Of Stability

Health News from Medical News Today — Wed, 25 Jan 2012 09:00:00 +0100

Human stem cells capable of giving rise to any fetal or adult cell type are known as pluripotent stem cells. It is hoped that such cells, the most well known being human embryonic stem cells (hESCs), can be used to generate cell populations with therapeutic utility. In this context, neural derivatives of hESCs are being tested in clinical trials... (Source: Health News from Medical News Today)

Transplantation of human central nervous system stem cells – neuroprotection in retinal degeneration

European Journal of Neuroscience — Wed, 25 Jan 2012 05:00:00 +0100

AbstractStem cells derived from the human brain and grown as neurospheres (HuCNS‐SC) have been shown to be effective in treating central neurodegenerative conditions in a variety of animal models. Human safety data in neurodegenerative disorders are currently being accrued. In the present study, we explored the efficacy of HuCNS‐SC in a rodent model of retinal degeneration, the Royal College of Surgeons (RCS) rat, and extended our previous cell transplantation studies to include an in‐depth examination of donor cell behavior and phenotype post‐transplantation. As a first step, we have shown that HuCNS‐SC protect host photoreceptors and preserve visual function after transplantation into the subretinal space of postnatal day 21 RCS rats. Moreover, cone photoreceptor density remain...

In schizophrenia research, a path to the brain through the nose

EurekAlert! - Social and Behavioral Science — Wed, 25 Jan 2012 05:00:00 +0100

(Elsevier) A significant obstacle to progress in understanding psychiatric disorders is the difficulty in obtaining living brain tissue for study so that disease processes can be studied directly. Recent advances in basic cellular neuroscience now suggest that, for some purposes, cultured neural stem cells may be studied in order to research psychiatric disease mechanisms. But where can one obtain these cells outside of the brain? (Source: EurekAlert! - Social and Behavioral Science)

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Avastin, Sutent increase breast cancer stem cells, U-M study shows

EurekAlert! - Medicine and Health — Wed, 25 Jan 2012 05:00:00 +0100

(University of Michigan Health System) Cancer treatments designed to block the growth of blood vessels were found to increase the number of cancer stem cells in breast tumors in mice, suggesting a possible explanation for why these drugs don't lead to longer survival, according to a new study by researchers at the University of Michigan Comprehensive Cancer Center. (Source: EurekAlert! - Medicine and Health)

Researchers induce Alzheimer's neurons from pluripotent stem cells

EurekAlert! - Social and Behavioral Science — Wed, 25 Jan 2012 05:00:00 +0100

(University of California - San Diego) Led by researchers at the University of California, San Diego School of Medicine, scientists have, for the first time, created stem cell-derived, in vitro models of sporadic and hereditary Alzheimer's disease, using induced pluripotent stem cells from patients with the much-dreaded neurodegenerative disorder. (Source: EurekAlert! - Social and Behavioral Science)

Stem cells: The right neighbour

Nature — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Ilya A. Shestopalov & Leonard I. Zon Different cell types produce signals that regulate the activity of blood-forming stem cells. A study shows that certain rare mesenchymal cells surrounding blood vessels are the main source of one such signal in mice. See Article p.457 (Source: Nature)

Endothelial and perivascular cells maintain haematopoietic stem cells

Nature — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Lei Ding, Thomas L. Saunders, Grigori Enikolopov & Sean J. Morrison Several cell types have been proposed to create niches for haematopoietic stem cells (HSCs). However, the expression patterns of HSC maintenance factors have not been systematically studied and no such factor has been conditionally deleted from any candidate niche cell. Thus, the cellular sources of (Source: Nature)

Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells

Nature AOP — Wed, 25 Jan 2012 05:00:00 +0100

Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells Nature advance online publication 25 January 2012. doi:10.1038/nature10821 Authors: Mason A. Israel, Shauna H. Yuan, Cedric Bardy, Sol M. Reyna, Yangling Mu, Cheryl Herrera, Michael P. Hefferan, Sebastiaan Van Gorp, Kristopher L. Nazor, Francesca S. Boscolo, Christian T. Carson, Louise C. Laurent, Martin Marsala, Fred H. Gage, Anne M. Remes, Edward H. Koo & Lawrence S. B. Goldstein Our understanding of Alzheimer’s disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent ...

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MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration [Research Papers]

Genes and Development — Wed, 25 Jan 2012 05:00:00 +0100

In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR and MRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury and muscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal muscle regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of...

A Chemical Genomics Screen to Discover Genes That Modulate Neural Stem Cell Differentiation

Journal of Biomolecular Screening — Wed, 25 Jan 2012 05:00:00 +0100

This study demonstrates that a phenotypic assay using cell type–specific antibody markers can be used for a large-scale compound screen to discover targets and pathways with impacts on differentiation of lineage-restricted precursor cells toward specific lineages. (Source: Journal of Biomolecular Screening)

A Gene Expression-Based Screening System for Compounds Influencing Differentiation of Mouse Embryonic Stem Cells

Journal of Biomolecular Screening — Wed, 25 Jan 2012 05:00:00 +0100

In this study, to classify a number of compounds, the authors established a gene expression–based screening system using mouse embryonic stem (ES) cells that monitored multiple parameters. ES cells were differentiated into three germ layers by embryoid body formation and then treated with the test compounds. Next, cellular changes were assessed by analyzing the expression of multiple genes with the multiplex quantitative reverse transcriptase polymerase chain reaction. By screening a library of pharmacologically active compounds with this system, the authors were able to classify 52 compounds that influenced the gene expression profile of ES cells. They also found that some compounds identified by screening could enhance osteogenic or adipogenic differentiation of human mesenchymal s...

Knockdown of Ubiquitin Ligases in Glioblastoma Cancer Stem Cells Leads to Cell Death and Differentiation

Journal of Biomolecular Screening — Wed, 25 Jan 2012 05:00:00 +0100

The cancer stem cell (CSC) hypothesis proposes that a subpopulation of CSCs is frequently responsible for chemotherapy resistance and metastasis and is now a point of attack for research into the next generation of therapeutics. Although many of these agents are directed at inducing CSC apoptosis (as well as the bulk tumor), some agents may also decrease cell "stemness" possibly through induction of differentiation. Ubiquitin ligases, critical to virtually all cellular signaling systems, alter the degradation or trafficking of most proteins in the cell, and indeed broad perturbation of this system, through inhibition of the proteosome, is a successful cancer treatment. The authors examined several glioblastoma stem cell isolates pre- and postdifferentiation to elucidate the phenotypic effe...

Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers

Breast Cancer Research — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions: The tumorigenic and metastatic potential of a subpopulation of mammary epithelial/tumor cells in MMT mice is endowed relatively early in mammary neoplasms and suggests a potential role for cancer stem cell sub-populations in metastasis. (Source: Breast Cancer Research)

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A Developmentally Controlled Competitive STAT5-PU.1 DNA Binding Mechanism Regulates Activity of the Ig κE3' Enhancer.

Journal of Immunology — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Hodawadekar S, Park K, Farrar MA, Atchison ML Abstract Stage-specific rearrangement of Ig H and L chain genes poses an enigma because both processes use the same recombinatorial machinery, but the H chain locus is accessible at the pro-B cell stage, whereas the L chain loci become accessible at the pre-B cell stage. Transcription factor STAT5 is a positive-acting factor for rearrangement of distal V(H) genes, but attenuation of IL-7 signaling and loss of activated STAT5 at the pre-B cell stage corresponds with Igκ locus accessibility and rearrangement, suggesting that STAT5 plays an inhibitory role at this locus. Indeed, loss of IL-7 signaling correlates with increased activity at the Igκ intron enhancer. However, the κE3' enhancer must also be regulated as this enhance...

Metformin Inhibits Growth of Thyroid Carcinoma Cells, Suppresses Self-Renewal of Derived Cancer Stem Cells, and Potentiates the Effect of Chemotherapeutic Agents.

The Journal of Clinical Endocrinology and Metabolism — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions:Metformin markedly diminished growth stimulation by insulin and showed an additive antimitogenic effect to chemotherapeutics agents. Therefore, our results suggest this drug as adjuvant treatment for thyroid cancer in type 2 diabetic patients. PMID: 22278418 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)

Isolation and Expansion of Human Limbal Stromal Niche Cells [Cornea]

Investigative Ophthalmology — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions. Limbal stromal niche cells expressing SC markers can be isolated and expanded to prevent differentiation and maintain clonal growth of limbal epithelial progenitors. (Source: Investigative Ophthalmology)

Macular Degeneration Improves With Embryonic Stem CellsMacular Degeneration Improves With Embryonic Stem Cells

Medscape Medical News Headlines — Wed, 25 Jan 2012 01:46:02 +0100

Before treatment, the 51-year-old graphic artist was legally blind, unable to read a single letter on a standard eye chart. Reuters Health Information (Source: Medscape Medical News Headlines)