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

近年来的研究表明，骨髓来源的内皮祖细胞（EPCs）作为生理和病理反应参与成人血管新生。新兴的临床前试验表明，EPCs在肢体和心肌缺血事件后归巢到新血管形成部位。在此基础上，内皮祖细胞有望成为缺血器官治疗应用的关键策略。我们假设在小鼠骨骼肌间隙中鉴定的骨骼肌特异性未成熟内皮EPCs（sk 34细胞= CD 34 +/CD 45-分数）可能作为治疗性血管生成对缺血性疾病有效。体外培养14 d后，Sk 34细胞形成鹅卵石状的内皮集落，乙酰化LDL-DiI染色，21 d后出现内皮管形成。将从EGFP转基因小鼠中分离的sk 34细胞移植到Balb/c裸小鼠缺血后肢后，通过肉眼、激光多普勒成像和组织学分析可以识别后肢缺血的改善。这些结果表明，肌肉特异性未成熟EPCs有助于改善组织缺血作为治疗性血管生成。

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..