Isolation and characterization of novel murine epiphysis derived mesenchymal stem cells

• Published in: PloS one 2012-04, Vol.7 (4), p.e36085-e36085
• Main Authors: Cheng, Chun-Chun, Lian, Wei-Shiung, Hsiao, Felix Shih-Hsiang, Liu, I-Hsuan, Lin, Shau-Ping, Lee, Yen-Hua, Chang, Chia-Chun, Xiao, Guan-Yu, Huang, Hsin-Yi, Cheng, Ching-Feng, Cheng, Winston Teng-Kuei, Wu, Shinn-Chih
• Format: Article
• Language: English
• Subjects: Adipocytes; Angiogenesis; Animal sciences; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - metabolism; Biocompatibility; Biology; Biomarkers - metabolism; Biomedical materials; Biotechnology; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; CD105 antigen; CD11b antigen; CD29 antigen; CD34 antigen; CD44 antigen; CD45 antigen; CD73 antigen; Cell culture; Cell Differentiation - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell Separation - methods; Cells, Cultured; Cellular Senescence - drug effects; Chondrocytes; Concanavalin A; Epiphyses - cytology; Epiphysis; Extremities - blood supply; Fibroblasts; Fracture Healing - drug effects; Fractures; Fractures, Bone - pathology; Fractures, Bone - therapy; Gangrene; Immune Tolerance - drug effects; Immunomodulation - drug effects; Immunophenotyping; Inflammation; Interferon-gamma - pharmacology; Interleukin 1; Interleukin 6; Ischemia; Ischemia - pathology; Ischemia - therapy; Major histocompatibility complex; Medical research; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - immunology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Mice; Mitogens; Models, Biological; Morphology; Multipotent Stem Cells - cytology; Multipotent Stem Cells - drug effects; Necrosis; Pediatrics; Rodents; Skin; Stem cells; Umbilical cord; Zoology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036085

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. 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. 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.