Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice
Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice
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DOI：
10.1126/scitranslmed.aaj2300
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发表时间：
2017-09-27
影响因子：
17.1
通讯作者：
Osafune, Kenji
中科院分区：
文献类型：
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作者：
Hitomi, Hirofumi;Kasahara, Tomoko;Osafune, Kenji
在慢性肾脏疾病(CKD)患者中，肾脏产生的促红细胞生成素(EPO)是造血系统的主要激素，最终导致严重贫血。尽管重组人促红细胞生成素治疗改善了慢性肾脏病患者的贫血，但并不总是会出现完全无波动的红细胞产生。我们建立了一种方法，通过修改先前报道的肝脏分化方案，从人诱导多能干细胞(HiPSCs)中产生EPO产生细胞。HIPSC-EPO细胞分泌的EPO蛋白在体外诱导人脐血祖细胞向红系分化。此外，将HiPSC-EPO细胞移植到腺嘌呤治疗所致的CKD小鼠体内，可以改善肾性贫血。因此，HiPSC-EPO细胞可能是一种有用的工具来阐明EPO的产生机制，并可能作为治疗肾性贫血的策略。
The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stemcells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia.