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  4. Establishment and Characterization of a Novel Mesenchymal Stem Cell Derived from Epiphysis and Their Potentials for Therapeutic Applications
 
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Establishment and Characterization of a Novel Mesenchymal Stem Cell Derived from Epiphysis and Their Potentials for Therapeutic Applications

Date Issued
2012
Date
2012
Author(s)
Cheng, Chun-Chun
URI
http://ntur.lib.ntu.edu.tw//handle/246246/257846
Abstract
While bone marrow (BM) is a rich source of mesenchymal stem cells (MSCs), previous studies have shown that MSCs derived from mouse BM were difficult to manipulate as compared to MSCs derived from other species. The objective of this study was to find stem cells of high proliferation and differentiation capacity as an alternative murine MSCs source from long bone except marrow tissue. In this study, we described a novel type of MSCs that migrates directly from the mouse epiphysis in culture. Epiphysis-derived MSCs (EMSCs) could be extensively expanded in plastic adherent culture, and they had a greater ability for clonogenic formation and cell proliferation than BMMSCs. Under specific induction conditions, EMSCs demonstrated multipotency through their ability to differentiate into adipocytes, osteocytes and chondrocytes. Immunophenotypic analysis demonstrated that EMSCs were positive for CD29, CD44, CD73, CD105, CD166, Sca-1 and SSEA-4, while negative for CD11b, CD31, CD34 and CD45. Notably, EMSCs did not express major histocompatibility complex class I (MHC I) or MHC II under our culture system. EMSCs also successfully suppressed the proliferation of splenocytes triggered by concanavalin A (Con A) or allogeneic splenocytes, and decreased the expression of IL-1, IL-6 and TNF-alpga in Con A-stimulated splenocytes suggesting their anti-inflammatory properties. For chemokine receptors analysis, EMSCs expressed CXCR7 while BMMSCs expressed CXCR4. Furthermore, EMSCs significantly enhanced VEGF, Flk-1 and PDGF expression under hypoxia condition. The results showed that EMSCs enhanced fracture repair, ameliorated necrosis in ischemic skin flap, and improved blood perfusion in hindlimb ischemia in the in vivo experiments. These results indicate that EMSCs, a new type of MSCs, are a preferable alternative for murine MSCs due to their better proliferation and differentiation potentialities.
Subjects
mouse
bone marrow
mesenchymal stem cells
immunosuppressive
bone fracture
skin flap
hindlimb ischemia
Type
thesis
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ntu-101-D96642002-1.pdf

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