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 stem cells (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.

慢性造血系统（CKD）患者肾脏中促红细胞生成素（EPO）的产生减少，这是造血系统的主要激素，最终导致严重的贫血。尽管重组人EPO治疗可改善CKD患者的贫血，但并非总是会出现无波动地恢复全血红细胞生成的情况。我们建立了一种方法，可以通过修改先前报道的肝分化方案从人诱导的多能干细胞（hiPSC）生成EPO产生细胞。这些细胞在低氧条件下，含有脯氨酰羟化酶结构域的酶抑制剂和类胰岛素生长因子1的作用下显示出增加的EPO表达和分泌。从hiPSC衍生的产生EPO的细胞（hiPSC-EPO）分泌的EPO蛋白在体外诱导人脐带血祖细胞的红细胞分化。此外，通过腺嘌呤治疗将hiPSC-EPO细胞移植到患有CKD的小鼠体内可改善肾性贫血。因此，hiPSC-EPO细胞可能是阐明EPO产生机理的有用工具，并且可以作为治疗肾性贫血的治疗策略。