Critical limb ischemia (CLI) is a state of severe peripheral artery disease, with no effective treatment. Cell therapy has been investigated as a therapeutic tool for CLI, and pericytes are promising therapeutic candidates based on their angiogenic properties. We firstly generated highly proliferative and immunosuppressive pericyte-like cells from embryonic stem (ES) cells. In order to enhance the angiogenic potential, we transduced the basic fibroblast growth factor (bFGF) gene into the pericyte-like cells and found a significant enhancement of angiogenesis in a Matrigel plug assay. Furthermore, we evaluated the bFGF-expressing pericyte-like cells in the previously established chronic hindlimb ischemia model in which bone marrow–derived MSCs were not effective. As a result, bFGF-expressing pericyte-like cells significantly improved blood flow in both laser Doppler perfusion imaging (LDPI) and dynamic contrast-enhanced MRI (DCE-MRI). These findings suggest that bFGF-expressing pericyte-like cells differentiated from ES cells may be a therapeutic candidate for CLI.

Graphical Abstract

中文翻译：

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移植转染碱性成纤维细胞生长因子的人胚胎干细胞衍生的周细胞样细胞可促进严重慢性后肢缺血小鼠的血管生成恢复

严重肢体缺血（CLI）是一种严重的外周动脉疾病状态，目前尚无有效的治疗方法。细胞疗法已被研究作为 CLI 的治疗工具，周细胞因其血管生成特性而成为有前途的治疗候选者。我们首先从胚胎干（ES）细胞中产生了高度增殖和免疫抑制的周细胞样细胞。为了增强血管生成潜力，我们将碱性成纤维细胞生长因子（bFGF）基因转导到周细胞样细胞中，并在基质胶栓塞测定中发现血管生成显着增强。此外，我们在先前建立的慢性后肢缺血模型中评估了表达 bFGF 的周细胞样细胞，在该模型中骨髓来源的 MSC 无效。结果，表达 bFGF 的周细胞样细胞显着改善了激光多普勒灌注成像 (LDPI) 和动态对比增强 MRI (DCE-MRI) 中的血流。这些发现表明，从 ES 细胞分化而来的表达 bFGF 的周细胞样细胞可能是 CLI 的治疗候选者。

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