Institute for Regenerative Medicine Applied Cell Therapy Research, Astellas Pharma Incorporated, 21 Miyukigaoka, Tsukuba-Shi, Ibaraki, 305-8585, Japan.
Joint Research Chair On Design for Advanced Medical System, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
J Cardiovasc Transl Res. 2024 Aug;17(4):828-841. doi: 10.1007/s12265-024-10496-9. Epub 2024 Feb 20.
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.
严重肢体缺血（CLI）是一种外周动脉疾病的严重状态，目前尚无有效的治疗方法。细胞治疗已被研究作为 CLI 的一种治疗工具，而周细胞因其血管生成特性而成为很有前途的治疗候选物。我们首先从胚胎干细胞（ES 细胞）中产生了高度增殖和免疫抑制的周细胞样细胞。为了增强其血管生成潜能，我们将碱性成纤维细胞生长因子（bFGF）基因转染到周细胞样细胞中，并在 Matrigel plugs 检测中发现了血管生成的显著增强。此外，我们在先前建立的慢性后肢缺血模型中评估了 bFGF 表达的周细胞样细胞，在该模型中，骨髓来源的间充质干细胞没有效果。结果表明，bFGF 表达的周细胞样细胞显著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，ES 细胞分化而来的 bFGF 表达的周细胞样细胞可能是 CLI 的一种治疗候选物。
