Saturday, January 16, 2010

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Surgical stem cell therapy for advanced heart failure patients.
January 16, 2010 at 7:37 AM

Surgical stem cell therapy for advanced heart failure patients.

Methodist Debakey Cardiovasc J. 2009;5(2):13-7

Authors: Bruckner BA, Ghodsizad A, Loebe M, Beyer E, Ramchandani M, Ruhparwar A, Karck M, Burchardt ER, Patel AN, Reardon M

PMID: 20073160 [PubMed - in process]

 

Differentiation factors that influence neuronal markers expression in vitro from human amniotic epithelial cells.
January 16, 2010 at 6:58 AM

Differentiation factors that influence neuronal markers expression in vitro from human amniotic epithelial cells.

Eur Cell Mater. 2010;19:22-9

Authors: Niknejad H, Peirovi H, Ahmadiani A, Ghanavi J, Jorjani M

The differentiation of neural cells from embryonic stem cells is influenced by several growth factors. Amniotic epithelial cells (AECs) share many of the same characteristics as embryonic stem cells, and therefore those factors may similarly affect the derivation of neural cells from AECs. In this study, we examined the differentiation of neural cells in vitro from AECs following AECs treatment with retinoic acid (RA), basic fibroblast growth factor (bFGF) as well as investigation of bFGF withdrawal on neuronal differentiation. We also studied whether blocking bone morphogenetic protein (BMP) signaling using its antagonist, noggin, affects the derivation of neuronal cells from AECs. The effects of serum on the rate of neural markers expression were also examined. Analysis of AECs derived neurons was performed at some neural markers expression level by immunocytochemistry. All cultures treated with noggin showed the higher levels of neural markers expression than n! oggin free cultures. Combined treatment with bFGF and RA showed the highest level of neural markers in all treatment groups with or without noggin. bFGF withdrawal did not promote expression of neural markers, while its maintenance increased the expression of these markers. Serum-free condition decreased the viability of cells but increased the rate of neural markers expression. These results show the capability of AECs to express neural cell markers and this ability is affected by some factors including serum, noggin, bFGF and RA.

PMID: 20077402 [PubMed - in process]

 

Behavior of Human Mesenchymal Stem Cells in Fibrin-Based Vascular Tissue Engineering Constructs.
January 16, 2010 at 6:58 AM

Behavior of Human Mesenchymal Stem Cells in Fibrin-Based Vascular Tissue Engineering Constructs.

Ann Biomed Eng. 2010 Jan 14;

Authors: O'Cearbhaill ED, Murphy M, Barry F, McHugh PE, Barron V

A limitation of current tissue engineering vascular graft technology is the provision of an expandable, autologous cell source. By harnessing the multipotency of mesenchymal stem cells (MSC), it is hoped that functional vascular cells can be produced. To date, a range of 2D and 3D environments have been investigated for the manipulation of MSC differentiation pathways. To this end, this study aims to test the hypothesis that MSC seeded in various fibrin gel environments will exhibit evidence of a smooth muscle cell (SMC) phenotype. Initially, a range of cell-seeding densities were screened for 2D and 3D fibrin constructs, where it was observed that a seeding densities of 500,000 cells/mL facilitated gel compaction without degradation or loss in cell viability. Additionally, positive expression of CD49, CD73, CD105 markers and negative expression of hemopoietic stem cell-associated CD34 and CD45 indicated that MSC phenotype was retained within the fibrin gel. Nonet! heless, a decrease in the gene expression of alpha-smooth cell actin and calponin was observed for MSC cultured in static 3D fibrin gels. Although a slight recovery was observed after 24 h mechanical stimulation, the fold-change remained significantly lower than that observed for cells cultured on 2D tissue culture plastic. While MSC differentiation toward a SMC appears possible in both 2D and 3D environments, scaffold architecture and mechanical stimulation undoubtedly play an important role in the creation of a functional SMC phenotype.

PMID: 20077010 [PubMed - as supplied by publisher]

 

Urologic Tissue Engineering in Pediatrics: From Nanostructures to Bladders.
January 16, 2010 at 6:58 AM

Urologic Tissue Engineering in Pediatrics: From Nanostructures to Bladders.

Pediatr Res. 2010 Jan 13;

Authors: Roth CC

The use of tissue engineering to develop new urinary bladder could have direct impact on children suffering from congenital bladder dysfunction. Current bladder tissue engineering protocols rely on scaffolds to support the ingrowth of new cells and the subsequent development of new tissues. The interaction between cells and scaffolds is mediated on the molecular level and nanotechnology is being investigated as a means to improve the biocompatibility of these scaffolds. In this review, we will discuss the current applications of nanotechnology for bladder tissue engineering; specifically, the use of selective degradation techniques and self-assembly molecules to create nano-features on existing scaffolds, the use of electrospinning to create de novo scaffolds, and the use of nanoparticles as a drug delivery system will be discussed. The use of nanotechnology has resulted in novel tissue engineering protocols, and is likely to be an important factor in the eventual! clinical application of tissue engineering for the urinary bladder.

PMID: 20075760 [PubMed - as supplied by publisher]

 

From stem cells to bone: phenotype acquisition, stabilization, and tissue engineering in animal models.
January 16, 2010 at 6:58 AM

From stem cells to bone: phenotype acquisition, stabilization, and tissue engineering in animal models.

ILAR J. 2009;51(1):42-61

Authors: Gordeladze JO, Reseland JE, Duroux-Richard I, Apparailly F, Jorgensen C

The regeneration of bone tissue depends on the concerted actions of a plethora of signals that recruit mesenchymal stem cells for lineage-specific differentiation, with cellular phenotypes serving various functions throughout their life span. The signals are conveyed in hormones, growth factors, and mechanical forces, all of which ensure proper modeling and remodeling. Both processes are secured by indigenous and programmed metabolism in osteoblasts/osteocytes as well as in other stem cell (SC)-derived cell types (e.g., osteoclasts, bone lining cells) involved in the remodeling of the subject tissue. The focus of this review is the concerted action of these signals as well as the regulatory and/or stabilizing control circuits exhibited by a class of small RNAs, designated microRNAs. We discuss an in vitro approach for ensuring proper phenotype acquisition as well as the choice of scaffolds and animal models for in vivo tissue repair. This approach includes selecti! on of SC niches to optimize bone formation in vivo, transcription factors important for osteoblastogenesis, the Wnt and Notch pathways of signaling, selection of delivery systems for gene therapy, use of appropriate matrices and scaffolds, in vivo mechanostimulation, choice of lesions to be repaired, and type of animal to use. We also discuss Wnt-related and SC-based treatment of osteoporosis. Throughout, we offer considerations for the selection of model systems and parameters to assess the entire procedure from initial SC selection to final bone repair, and conclude with a table summarizing our recommendations.

PMID: 20075497 [PubMed - in process]

 

Effects of bone morphogenetic protein-2 on proliferation and angiogenesis in oral squamous cell carcinoma.
January 16, 2010 at 6:58 AM

Effects of bone morphogenetic protein-2 on proliferation and angiogenesis in oral squamous cell carcinoma.

Int J Oral Maxillofac Surg. 2010 Jan 12;

Authors: Gao Q, Tong W, Luria JS, Wang Z, Nussenbaum B, Krebsbach PH

Experimental data and limited patient experience suggest that rhBMP-2 can be used to regenerate bone in acquired segmental defects of the mandible. Most of these defects are caused by resection of oral squamous cell carcinoma (OSCC) and the biologic effects of rhBMP-2 on these carcinoma cells are unknown. The objective of this study was to determine whether rhBMP-2 produces adverse effects on proliferation and angiogenesis in OSCC, two biologic processes critical to tumor formation. In vitro studies included treating OSCC cells with rhBMP-2 or an adenoviral vector containing the cDNA for BMP-2. In vivo studies involved co-transplantation of OSCC cells with bone marrow stromal cells genetically modified to over express BMP-2, to mimic a clinically relevant scenario for regenerating bone using cell-based therapy in a wound containing microscopic residual disease. Proliferation, as measured by a MTT assay in vitro and tumor growth in vivo was not affected by treatmen! t with BMP-2. Angiogenesis, measured by secretion of the proangiogenic molecules VEGF and IL-8 in vitro and microvessel density in vivo, was not affected. Exposure of OSCC cells to BMP-2 does not stimulate proliferation or angiogenesis. Further studies are needed before using rhBMP-2 for bone tissue engineering in oral cancer-related defects.

PMID: 20074910 [PubMed - as supplied by publisher]

 

Synchrotron X-Ray Bio-imaging of Bone Regeneration by Artificial Bone Substitute of MGSB and Hyaluronate Hydrogels.
January 16, 2010 at 6:58 AM

Synchrotron X-Ray Bio-imaging of Bone Regeneration by Artificial Bone Substitute of MGSB and Hyaluronate Hydrogels.

Tissue Eng Part C Methods. 2010 Jan 14;

Authors: Yeom J, Chang S, Park JK, Je JH, Yang DJ, Choi SK, Shin HI, Lee SJ, Shim JH, Cho DW, Hahn SK

Synchrotron X-ray bioimaging was successfully carried out to visualize the bone regeneration by a novel artificial bone substitute of bioactive MegaGen Synthetic Bone (MGSB) and hyaluronate (HA) hydrogels. A biphasic calcium phosphate of MGSB was prepared by chemical precipitation method with a porous spherical morphology. On the basis of the fact that HA plays important roles in bone regeneration, and promotes the differentiation, vascularization, and migration of stem cells, HA-Cystamine (CYS) hydrogels with cleavable disulfide linkages were prepared to supply HA continuously for effective bone regeneration by their controlled degradation in vivo. Among seven different samples using Bio-OSS(R), MGSB, and/or several kinds of HA hydrogels, MGSB/HA-CYS hydrogels resulted in the most significant bone regeneration in the calvarial critical bone deffect of New Zealand white rabbits. Histological and histomorphometric analyses revealed that the bone regeneration by MGS! B/HA-CYS hydrogels was as high as 43% occupying 71% of the bone defect area with MGSB in the form of a calvarial bone plate in 4 wks. After that, MGSB was bioabsorbed and replaced gradually with regenerated bones as observed in 8 wks. Synchrotron X-ray imaging clearly confirmed the effective bone regeneration by MGSB/HA-CYS hydrogels visualizing 3D micron-scale morphologies of regenerated bones being interconnected with MGSB. In addition, sequential non-distructive synchrotron X-ray tomographic analysis results from anterior to posterior of the samples were well matched with the histomorphometric analysis results. The clinically feasible artificial bone substitutes of MGSB/HA-CYS hydrogels will be investigated further for various bone tissue engineering applications using the synchrotron X-ray bio-imaging systems.

PMID: 20073984 [PubMed - as supplied by publisher]

 

Three-dimensional plotter technology for fabricating polymeric scaffolds with micro-grooved surfaces.
January 16, 2010 at 6:58 AM

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Three-dimensional plotter technology for fabricating polymeric scaffolds with micro-grooved surfaces.

J Biomater Sci Polym Ed. 2009;20(14):2089-101

Authors: Son J, Kim G

Various mechanical techniques have been used to fabricate biomedical scaffolds, including rapid prototyping (RP) devices that operate from CAD files of the target feature information. The three-dimensional (3-D) bio-plotter is one RP system that can produce design-based scaffolds with good mechanical properties for mimicking cartilage and bones. However, the scaffolds fabricated by RP have very smooth surfaces, which tend to discourage initial cell attachment. Initial cell attachment, migration, differentiation and proliferation are strongly dependent on the chemical and physical characteristics of the scaffold surface. In this study, we propose a new 3-D plotting method supplemented with a piezoelectric system for fabricating surface-modified scaffolds. The effects of the physically-modified surface on the mechanical and hydrophilic properties were investigated, and the results of cell culturing of chondrocytes indicate that this technique is a feasible new metho! d for fabricating high-quality 3-D polymeric scaffolds.

PMID: 19874679 [PubMed - indexed for MEDLINE]

 

Surface characterization of extracellular matrix scaffolds.
January 16, 2010 at 6:58 AM

Related Articles

Surface characterization of extracellular matrix scaffolds.

Biomaterials. 2010 Jan;31(3):428-37

Authors: Brown BN, Barnes CA, Kasick RT, Michel R, Gilbert TW, Beer-Stolz D, Castner DG, Ratner BD, Badylak SF

Extracellular matrix (ECM) scaffolds prepared from different tissue sources or using different methods have been demonstrated to have distinctive effects upon cell adhesion patterns and the ability to support and maintain differentiated phenotypes. It is unknown whether the molecular composition or the ultrastructure of the ECM plays a greater role in determining the phenotype of the cells with which it comes into contact. However, when implanted, the topology and ligand landscape of the material will determine the host molecules that bind and the type and behavior of cells that mediate the host response. Therefore, a comprehensive understanding of surface characteristics is essential in the design of scaffolds for specific clinical applications. The surface characteristics of ECM scaffolds derived from porcine urinary bladder, small intestine, and liver as well as the effects of two commonly used methods of chemical cross-linking upon UBM were investigated. Elect! ron microscopy and time of flight secondary ion mass spectroscopy were used to examine the surface characteristics of the scaffolds. The results show that ECM scaffolds have unique morphologic and structural properties which are dependant on the organ or tissue from which the scaffold is harvested. Furthermore, the results show that the surface characteristics of an ECM scaffold are changed through chemical cross-linking.

PMID: 19828192 [PubMed - indexed for MEDLINE]

 

Concentrated collagen hydrogels as dermal substitutes.
January 16, 2010 at 6:58 AM

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Concentrated collagen hydrogels as dermal substitutes.

Biomaterials. 2010 Jan;31(3):481-90

Authors: Helary C, Bataille I, Abed A, Illoul C, Anglo A, Louedec L, Letourneur D, Meddahi-Pellé A, Giraud-Guille MM

Collagen hydrogels first appeared promising for skin repair. Unfortunately, their extensive contraction and their poor mechanical properties constituted major disadvantages toward their utilization as permanent graft. The present study has investigated a way to correct these drawbacks by increasing the collagen concentration in controlled conditions. Concentrated collagen hydrogels (CCH) at 1.5, 3 and 5mg/ml were obtained. The effect of raised collagen concentration on contraction, cell growth and remodeling activities was evaluated for 21 days in culture. Subsequently, in vivo integration of CCH and normal collagen hydrogels (NCH) was assessed. Compared to NCH, CCH contraction was delayed and smaller. At day 21, surface area of CCH at 3mg/ml was 18 times more important than that of NCH. Whatever the initial fibroblast density, CCH favored cell growth that reached about 10 times the initial cell number at day 21; cell proliferation was inhibited in NCH. Gelatinase! A activities appeared lower in CCH than within NCH. In vivo studies in rats revealed a complete hydrolysis of NCH 15 days after implantation. In contrast, CCH at 3mg/ml was still present after 30 days. Moreover, CCH showed cell colonization, neovascularization and no severe inflammatory response. Our results demonstrate that concentrated collagen hydrogels can be considered as new candidates for dermal substitution because they are is easy to handle, do not contract drastically, favor cell growth, and can be quickly integrated in vivo.

PMID: 19811818 [PubMed - indexed for MEDLINE]

 

Affinity study of novel gelatin cell carriers for fibronectin.
January 16, 2010 at 6:58 AM

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Affinity study of novel gelatin cell carriers for fibronectin.

Macromol Biosci. 2009 Nov 10;9(11):1105-15

Authors: Van Vlierberghe S, Vanderleyden E, Dubruel P, De Vos F, Schacht E

In the present work, the gelatin/fibronectin affinity was evaluated using SPR, QCM and radiolabelling. The results indicate that type A gelatin films possess a higher affinity for Fn compared to type B gelatin. This is due to a combined hydrophobic and electrostatic interaction between gelatin type A and Fn. In a second part, the affinity of Fn for porous gelatin scaffolds was evaluated. The scaffolds were prepared by a cryogenic treatment and subsequent freeze-drying yielding type I and type II scaffolds which possess different pore geometries/sizes. The results indicate that the Fn density on the scaffolds can be fine-tuned by varying the Fn concentration, the gelatin type (A vs. B), the pore size/geometry (type I vs. type II scaffolds).

PMID: 19626719 [PubMed - indexed for MEDLINE]

 

Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation.
January 16, 2010 at 6:31 AM

Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation.

Cell Death Differ. 2010 Jan 15;

Authors: Mora-Castilla S, Tejedo JR, Hmadcha A, Cahuana GM, Martín F, Soria B, Bedoya FJ

Exposure of mouse embryonic stem (mES) cells to high concentrations of chemical nitric oxide (NO) donors promotes differentiation, but the mechanisms involved in this process at the gene expression level are poorly defined. In this study we report that culture of mES cells in the presence of 0.25-1.0 mM diethylenetriamine nitric oxide adduct (DETA-NO) leads to downregulation of Nanog and Oct4, the two master genes involved in the control of the pluripotent state. This action of NO was also apparent in the human ES cell line, HS 181. The suppressive action of NO on Nanog gene depends on the activation of p53 repressor protein by covalent modifications, such as pSer15, pSer315, pSer392 and acetyl Lys 379. NO-induced repression of Nanog is also associated with binding of trimethylated histone H3 and pSer315 p53 to its promoter region. In addition, exposure to 0.5 mM DETA-NO induces early differentiation events of cells with acquisition of epithelial morphology and ex! pression of markers of definitive endoderm, such as FoxA2, Gata4, Hfn1-beta and Sox 17. This phenotype was increased when cells were treated with valproic acid (VPA) for 10 days.Cell Death and Differentiation advance online publication, 15 January 2010; doi:10.1038/cdd.2009.204.

PMID: 20075941 [PubMed - as supplied by publisher]

 

A "season of light" in stem cell research and regenerative medicine: observations on recent developments.
January 16, 2010 at 6:31 AM

A "season of light" in stem cell research and regenerative medicine: observations on recent developments.

ILAR J. 2009;51(1):85-7

Authors: Womack JE

PMID: 20075501 [PubMed - in process]

 

Practical considerations in regenerative medicine research: IACUCs, ethics, and the use of animals in stem cell studies.
January 16, 2010 at 6:31 AM

Practical considerations in regenerative medicine research: IACUCs, ethics, and the use of animals in stem cell studies.

ILAR J. 2009;51(1):82-4

Authors: Vandewoude S, Rollin BE

PMID: 20075500 [PubMed - in process]

 

Chimeric animal models in human stem cell biology.
January 16, 2010 at 6:31 AM

Chimeric animal models in human stem cell biology.

ILAR J. 2009;51(1):62-73

Authors: Glover JC, Boulland JL, Halasi G, Kasumacic N

The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the c! hicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

PMID: 20075498 [PubMed - in process]

 

The use of animals in human stem cell research: past, present, and future.
January 16, 2010 at 6:31 AM

The use of animals in human stem cell research: past, present, and future.

ILAR J. 2009;51(1):1-2

Authors: Gearhart JD, Addis RC

PMID: 20075494 [PubMed - in process]

 

The California Stem Cell Initiative: Persuasion, Politics, and Public Science.
January 16, 2010 at 6:31 AM

The California Stem Cell Initiative: Persuasion, Politics, and Public Science.

Am J Public Health. 2010 Jan 14;

Authors: Adelson JW, Weinberg JK

The California Institute for Regenerative Medicine (CIRM) was created by a California ballot initiative to make stem cell research a constitutional right, in response to Bush administration restrictions on stem cell research. The initiative created a taxpayer-funded, multibillion-dollar institution, intended to advance public health by developing cures and treatments for diabetes, cancer, paralysis, and other conditions. The initiative has been highly controversial among stakeholders and watchdog groups concerned with organizational transparency, accountability, and the ethics of stem cell research. We interviewed major stakeholders-both supporters and opponents-and analyzed documents and meeting notes. We found that the CIRM has overcome start-up challenges, been selectively influenced by criticism, and adhered to its core mission.

PMID: 20075315 [PubMed - as supplied by publisher]

 

microRNA, Cell Cycle, and Human Breast Cancer.
January 16, 2010 at 6:31 AM

microRNA, Cell Cycle, and Human Breast Cancer.

Am J Pathol. 2010 Jan 14;

Authors: Yu Z, Baserga R, Chen L, Wang C, Lisanti MP, Pestell RG

The discovery of microRNAs as a novel class of gene expression regulators has led to a new strategy for disease diagnostics and therapeutics. Cell cycle, cell proliferation, and tumorigenesis are all regulated by microRNAs. Several general principles linking microRNAs and cancer have been recently reviewed; therefore, the current review focuses specifically on the perspective of microRNAs in control of cell cycle, stem cells, and heterotypic signaling, as well as the role of these processes in breast cancer. Altered abundance of cell cycle regulation proteins and aberrant expression of microRNAs frequently coexist in human breast cancers. Altered microRNA expression in breast cancer cell lines is associated with altered cell cycle progression and cell proliferation. Indeed, recent studies have demonstrated a causal role for microRNA in governing breast tumor suppression or collaborative oncogenesis. This review summarizes the current understanding of the role for ! microRNA in regulating the cell cycle and summarizes the evidence for aberrant microRNA expression in breast cancer. The new evidence for microRNA regulation by annotated genes and the involvement of microRNA in breast cancer metastasis are discussed, as is the potential for microRNA to improve breast cancer diagnosis and therapy.

PMID: 20075198 [PubMed - as supplied by publisher]

 

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells.
January 16, 2010 at 6:31 AM

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells.

Cell Stem Cell. 2010 Jan 8;6(1):59-70

Authors: Chng Z, Teo A, Pedersen RA, Vallier L

Human embryonic stem cells (hESCs) rely on fibroblast growth factor and Activin-Nodal signaling to maintain their pluripotency. However, Activin-Nodal signaling is also known to induce mesendoderm differentiation. The mechanisms by which Activin-Nodal signaling can achieve these contradictory functions remain unknown. Here, we demonstrate that Smad-interacting protein 1 (SIP1) limits the mesendoderm-inducing effects of Activin-Nodal signaling without inhibiting the pluripotency-maintaining effects exerted by SMAD2/3. In turn, Activin-Nodal signaling cooperates with NANOG, OCT4, and SOX2 to control the expression of SIP1 in hESCs, thereby limiting the neuroectoderm-promoting effects of SIP1. Similar results were obtained with mouse epiblast stem cells, implying that these mechanisms are evolutionarily conserved and may operate in vivo during mammalian development. Overall, our results reveal the mechanisms by which Activin-Nodal signaling acts through SIP1 to regul! ate the cell-fate decision between neuroectoderm and mesendoderm in the progression from pluripotency to primary germ layer differentiation.

PMID: 20074535 [PubMed - as supplied by publisher]

 

Intermediate-Term Hematopoietic Stem Cells with Extended but Time-Limited Reconstitution Potential.
January 16, 2010 at 6:31 AM

Intermediate-Term Hematopoietic Stem Cells with Extended but Time-Limited Reconstitution Potential.

Cell Stem Cell. 2010 Jan 8;6(1):48-58

Authors: Benveniste P, Frelin C, Janmohamed S, Barbara M, Herrington R, Hyam D, Iscove NN

Sustained blood cell production depends on divisions by hematopoietic stem cells (HSCs) that yield both differentiating progeny as well as new HSCs via self-renewal. Differentiating progeny remain capable of self-renewal, but only HSCs sustain self-renewal through successive divisions securely enough to maintain clones that persist life-long. Until recently, the first identified next stage consisted of "short-term" reconstituting cells able to sustain clones of differentiating cells for only 4-6 weeks. Here we expand evidence for a numerically dominant "intermediate-term" multipotent HSC stage in mice whose clones persist for 6-8 months before becoming extinct and that are separable from both short-term as well as permanently reconstituting "long-term" HSCs. The findings suggest that the first step in stem cell differentiation consists not in loss of initial capacity for serial self-renewal divisions, but rather in loss of mechanisms that stabilize self-renewing b! ehavior throughout successive future stem cell divisions.

PMID: 20074534 [PubMed - as supplied by publisher]

 

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