Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Drug Discovery Research, Astellas Pharma Inc, Tsukuba, Ibaraki, Japan.
Sci Rep. 2018 Apr 23;8(1):6375. doi: 10.1038/s41598-018-24714-3.
Cell therapy using renal progenitors differentiated from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) has the potential to significantly reduce the number of patients receiving dialysis therapy. However, the differentiation cultures may contain undifferentiated or undesired cell types that cause unwanted side effects, such as neoplastic formation, when transplanted into a body. Moreover, the hESCs/iPSCs are often genetically modified in order to isolate the derived renal progenitors, hampering clinical applications. To establish an isolation method for renal progenitors induced from hESCs/iPSCs without genetic modifications, we screened antibodies against cell surface markers. We identified the combination of four markers, CD9CD140aCD140bCD271, which could enrich OSR1SIX2 renal progenitors. Furthermore, these isolated cells ameliorated renal injury in an acute kidney injury (AKI) mouse model when used for cell therapy. These cells could contribute to the development of hiPSC-based cell therapy and disease modeling against kidney diseases.
使用源自人类胚胎干细胞 (hESC) 或诱导多能干细胞 (hiPSC) 的肾祖细胞进行细胞治疗，有可能显著减少接受透析治疗的患者数量。然而，分化培养物可能含有未分化或不需要的细胞类型，当移植到体内时会引起不良反应，例如肿瘤形成。此外，为了分离衍生的肾祖细胞，hESC/iPSC 通常经过基因修饰，从而阻碍了临床应用。为了建立一种不进行基因修饰即可从 hESC/iPSC 诱导分离肾祖细胞的方法，我们筛选了针对细胞表面标志物的抗体。我们确定了四种标志物（CD9、CD140a、CD140b 和 CD271）的组合，可以富集 OSR1SIX2 肾祖细胞。此外，当用于细胞治疗时，这些分离的细胞可改善急性肾损伤 (AKI) 小鼠模型中的肾损伤。这些细胞可能有助于基于 hiPSC 的细胞治疗和针对肾脏疾病的疾病建模的发展。
