筋肉組織特異的血管内皮前駆細胞を用いた血管再生療法の開発

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Recent evidences suggest that endothelial progenitor cells (EPCs) derived from bone marrow contribute to de novo vessel formation in adults occurring as physiological and pathological responses. Emerging preclinical trials have shown that EPCs home to sites of neovascularization after ischemic events in limb and myocardium. On the basis of these aspects, EPCs are expected to develop as a key strategy of therapeutic applications for the ischemic organs. We hypothesized that skeletal muscle specific immature endothelial EPCs identified in the interstitial spaces of murine skeletal muscle (sk34 cells= CD34+/CD45-fraction) may be effective for the ischemic diseases as therapeutic vasculogenesis. Cultured Sk34cells formed endothelial colonies with the shape of cobblestone appearance stained with acetylated LDL-DiI after 14 days, and presented endothelial tube formation after 21 days in vitro. Following transplantation of sk34cells isolated from EGFP transgenic mice into ischemic hindlimb of Balb/c nude mice, the improvement of hindlimb ischemia could be recognized by macroscopic, laser doppler imaging, and histological analyses. These findings presented that muscle specific immature EPCs contribute to the improvement of tissue ischemia as therapeutic vasculogenesis..