Background: While bone marrow (BM) is a rich source of mesenchymal stem cells (MSCs), previous studies have shown that MSCs derived from mouse BM (BMMSCs) were difficult to manipulate as compared to MSCs derived from other species. The objective of this study was to find an alternative murine MSCs source that could provide sufficient MSCs. Methodology/Principal Findings: 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-α in Con A-stimulated splenocytes suggesting their anti-inflammatory properties. Moreover, EMSCs enhanced fracture repair, ameliorated necrosis in ischemic skin flap, and improved blood perfusion in hindlimb ischemia in the in vivo experiments. Conclusions/Significances: These results indicate that EMSCs, a new type of MSCs established by our simple isolation method, are a preferable alternative for mice MSCs due to their better growth and differentiation potentialities.
|State||Published - Apr 27 2012|
Bibliographical noteFunding Information:
We would like to thank Prof. Osamu Ohneda (Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba) and Dr. Kenichi Kimura (Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba) for their invaluable advice and technical assistance, Dr. Georgina To'a Salazar (Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba) for discussions and comments on the manuscript, and Taiwan Mouse Clinic which is funded by National Research Program for Biopharmaceuticals (NRPB) at the National Science Council (NSC) of Taiwan for technical support in experiment.
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