Isolation and identification of tissue stem cell for clinical application

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Although tissue stem cells contribute to regeneration of tissue and has therapeutic potentials for clinical application of regenerative medicine, the use of the cells has some concerns including low proliferating capacity and low transplantable capacity as compared with ES cells. This study also reveals that ciliary body-derived tissue stem cells have an potential ability to differentiate into neural cells due to cell-aggregation without cell-proliferation. To overcome these issues, we identified and isolated a novel cell population, Albumin(ALB)+a-smooth muscle actin(a-SMA)VEGFR2+ cells, which also expressed the ES cell-expressing markers, and we also found out that the cells could differentiate to a-SMA+ smooth muscle cells or CD31+ vascular endothelial cells in the presence of PDGF-BB and VEGF, and could differentiate to ALB+ hepatocytes or CK18+ bile duct cells in the presence of HGF and EGF in vitro. Moreover, we found out that the non-stimulated VEGFR2+ cells could differentiate to α-SMA+ smooth muscle cells or CD31+ vascular endothelial cells, and HGF+EGF-stimulated VEGFR2+ cells could differentiate to hepatocytes or bile duct cells in vivo, when the cells were inoculated into subcapsule of spleens in partial hepatectomized adult mice.Furthermore, we identified and isolated a cord blood-derived cell population, CD45-CD133+CD34+VEGFR2+ cells, which could form colonies and differentiate to CD133-CD31+ vascular endothelial cells or α-SMA+ smooth muscle cells in the presence of VEGF, IGF, FGF-2,and/or PDGF-BB in vitro. In therapeutic cell transplantation for clinical setting, although there is a concern about rejection by sensitized allo-reactive memory T cells, the cord blood-derived CD45-VEGFR2+ cells has a potential source as endothelial progenitor cell (EPC), because we indicated that CCL2 was highly expressed in the ischemic muscular tissues using our murine limb ischemia models.