Transplantation of freshly isolated adipose tissue-derived regenerative cells enhances angiogenesis in a murine model of hind limb ischemia
Transplantation of freshly isolated adipose tissue-derived regenerative cells enhances angiogenesis in a murine model of hind limb ischemia
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DOI：
10.2220/biomedres.34.23
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发表时间：
2013-02-01
影响因子：
1.2
通讯作者：
Hisatome, Ichiro
中科院分区：
文献类型：
--
作者：
Harada, Yusuke;Yamamoto, Yasutaka;Hisatome, Ichiro
治疗性血管生成已成为严重缺血性心血管疾病的最有前途的治疗方法之一，没有可选的治疗。一些研究者已经报道，将培养的脂肪来源的再生细胞（cADRC）移植到缺血组织促进新血管形成和血液灌注恢复;然而，使用培养的细胞的细胞疗法具有若干限制。为了解决这个问题，将从刘易斯大鼠获得的新鲜分离的ADRC（fADRC）的血管生成能力与cADRC进行体内和体外比较。流式细胞术分析表明，fADRC含有几种细胞类型，如内皮祖细胞和内皮细胞;然而，这些细胞在cADRC中的比例非常小。与盐水注射组相比，小鼠中fADRCs的移植显著改善了移植缺血肢体中的血液灌注、毛细血管密度和几种血管生成因子的产生，而在cADRCs注射组中未观察到这些作用。在体外研究中，fADRC还显示出比cADRC显著更高的血管生成因子表达水平。此外，在体外管形成测定中，fADRC比cADRC更显著地刺激管形成。这些结果表明，fADRC具有有效的血管生成能力，并且它们作为基于细胞的治疗性血管生成的来源比cADRC或其他干/祖细胞更有价值。
Therapeutic angiogenesis has emerged as one of the most promising therapies for severe ischemic cardiovascular diseases with no optional therapy. Several investigators have reported that transplantation of cultured adipose-derived regenerative cells (cADRCs) to ischemic tissues promotes neovascularization and blood perfusion recovery; however, cell therapy using cultured cells has several restrictions. To resolve this problem, the angiogenic capacity of freshly isolated ADRCs (fADRCs) obtained from Lewis rats was compared with cADRCs, both in vivo and in vitro. Flow cytometric analysis showed that fADRCs contained several cell types such as endothelial progenitor cells and endothelial cells; however, these cells were present in a very small proportion in cADRCs. Transplantation of fADRCs in mice significantly improved blood perfusion, capillary density, and production of several angiogenic factors in transplanted ischemic limbs compared with a saline-injected group, whereas these effects were not observed in the cADRCs-injected group. fADRCs also showed significantly higher expression levels of angiogenic factors than cADRCs in the in vitro study. Furthermore, fADRC stimulated tube formation more remarkably than cADRC in an in vitro tube formation assay. These results suggested that fADRCs have an effective angiogenic capacity, and they would be more valuable as a source for cell-based therapeutic angiogenesis than cADRCs or other stem/progenitor cells.