Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice

Hirofumi Hitomi, Tomoko Kasahara, Naoko Katagiri, Azusa Hoshina, Shin Ichi Mae, Maki Kotaka, Takafumi Toyohara, Asadur Rahman, Daisuke Nakano, Akira Niwa, Megumu K. Saito, Tatsutoshi Nakahata, Akira Nishiyama, Kenji Osafune

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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 EPOtreatment improves anemia in patientswith CKD, returning to full red blood cell productionwithout 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 fromhiPSC-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.

Original languageEnglish
Article numbereaaj2300
JournalScience Translational Medicine
Volume9
Issue number409
DOIs
Publication statusPublished - 2017 Sep 27

ASJC Scopus subject areas

  • Medicine(all)

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