|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | The Use of Human Embryonic Stem Cells in Drug Discovery. Clin Pharmacol Ther. 2011 May;89(5):641-643 Authors: Esteso P, Gearhart JD PMID: 21512522 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Diet-induced obesity in Sca-1 KO mice. Stem Cells Dev. 2011 Apr 21; Authors: Staszkiewicz J, Gimble J, Dietrich MA, Gawronska-Kozak B Stem Cell Antigen-1 (Sca-1) is a member of the Ly6 family and has served as a marker for the identification of stem cells in various tissues, including fat depots. In vitro and in vivo studies suggest the possible involvement of Sca-1 in adipogenic differentiation and link Sca-1 antigenicity with adipocyte progenitors. Previously we showed that Sca-1 enriched populations of ear mesenchymal stem cells possess enhanced capacity to differentiate into adipocytes. Additionally we determined the natural frequency and localization of Sca-1 positive progenitor/stem cells in brown and white fat in situ. The present study addressed the question whether Sca-1 deficiency alters the white adipose tissue response to a high saturated fat diet. Our results show that Sca-1 null mice (Sca-1-/-) fed high fat diet developed obesity equally well as wild type mice suggesting either an indirect in vivo effect of Sca-1 or a compensatory response to Sca-1 deficiency. However, contrary to wild type mice, high fat diet fed Sca-1-/- mice showed no alterations in serum adipocytokines. The data leads to the conclusion that Sca-1 is either redundant or a non-essential marker of adipose progenitor/stem cells. Nevertheless, since Sca-1 deficient mice displayed elevated blood glucose at fasting, exhibited glucose intolerance and insulin resistance, Sca-1 has subtle effects on adipose function. Thus, the Sca-1 deficient mice may provide a useful model for metabolic studies. PMID: 21510817 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | NMR-Based Metabolomic Analysis of the Molecular Pathogenesis of Therapy-Related Myelodysplasia/Acute Myeloid Leukemia. J Proteome Res. 2011 Apr 21; Authors: Cano KE, Li L, Bhatia S, Bhatia R, Forman SJ, Chen Y Hematopoietic stem cell transplantation is the oldest and successful form of stem cell therapy. High dose therapy (HDT) followed by hematopoietic stem cell transplantation allows physicians to administer increased amounts of chemotherapy and/or radiation while minimizing negative side effects such as damage to blood-producing bone marrow cells. Although HDT is successful in treating a wide range of cancers, it leads to lethal therapy-related myelodysplasia syndrome or acute myeloid leukemia (t-MDS/AML) in 5-10% of patients undergoing autologous hematopoietic cell transplantation for Hodgkin lymphoma and non-Hodgkin lymphoma. In this study, we carried out metabolomic analysis of peripheral blood stem cell samples collected in a cohort of patients before hematopoietic cell transplantation in order to gain insights into the molecular and cellular pathogenesis of t-MDS. Nonparametric tests and multivariate analyses were used to compare the metabolite concentrations in samples from patients that developed t-MDS within 5 years of transplantation and the patients that did not. The results suggest that the development of t-MDS is associated with dysfunctions in cellular metabolic pathways. The top canonical pathways suggested by the metabolomic analysis include alanine and aspartate metabolism, glyoxylate and dicarboxylate metabolism, phenylalanine metabolism, citrate acid cycle, and aminoacyl-t-RNA biosynthesis. Dysfunctions in these pathways indicate mitochondrial dysfunction that would result in decreased ability to detoxify reactive oxygen species generated by chemo and radiation therapy, therefore leading to cancer causing mutations. These observations suggest predisposing factors for the development of t-MDS. PMID: 21510650 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hydrogels for the Repair of Articular Cartilage Defects. Tissue Eng Part B Rev. 2011 Apr 21; Authors: Spiller KL, Maher SA, Lowman AM The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, 3-D polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells. Hydrogels have been prepared from naturally-derived and synthetic polymers, as cell-free implants and as tissue engineering scaffolds, and with controlled degradation profiles and release of stimulatory growth factors. Using hydrogels, cartilage tissue has been engineered in vitro that has similar mechanical properties to native cartilage. This review summarizes the advancements that have been made in determining the potential of hydrogels to replace damaged cartilage or support new tissue formation as a function of specific design parameters, such as the type of polymer, degradation profile, mechanical properties and loading regimen, source of cells, cell-seeding density, controlled release of growth factors, and strategies to cause integration with surrounding tissue. Some key challenges for clinical translation remain, including limited information on the mechanical properties of hydrogel implants or engineered tissue that are necessary to restore joint function, and the lack of emphasis on the ability of an implant to integrate in a stable way with the surrounding tissue. Future studies should address the factors that affect these issues, while using clinically relevant cell sources and rigorous models of repair. PMID: 21510824 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Physical properties of mesenchymal stem cells are coordinated by the perinuclear actin cap. Biochem Biophys Res Commun. 2011 Apr 9; Authors: Kihara T, Haghparast SM, Shimizu Y, Yuba S, Miyake J Mesenchymal stem cells (MSCs) have been extensively investigated for their applications in regenerative medicine. Successful use of MSCs in cell-based therapies will rely on the ability to effectively identify their properties and functions with a relatively non-destructive methodology. In this study, we measured the surface stiffness and thickness of rat MSCs with atomic force microscopy and clarified their relation at a single-cell level. The role of the perinuclear actin cap in regulating the thickness, stiffness, and proliferative activity of these cells was also determined by using several actin cytoskeleton-modifying reagents. This study has helped elucidate a possible link between the physical properties and the physiological function of the MSCs, and the corresponding regulatory role of the actin cytoskeleton. PMID: 21510920 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |  | |  | |  |
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