Erythropoietic properties of human induced pluripotent stem cells-derived red blood cells in immunodeficient mice

Jiusheng Deng, Moira Lancelot, Ryan Jajosky, Qiaomei Deng, Kristin Deeb, Natia Saakadze, Yongxing Gao, David Jaye, Senquan Liu, Sean R. Stowell, Linzhao Cheng, John D. Roback

Research output: Contribution to journalArticlepeer-review


Transfusion of red blood cells (RBCs) is a life-saving intervention for anemic patients. Human induced pluripotent stem cells (iPSC) have the capability to expand and differentiate into RBCs (iPSC-RBCs). Here we developed a murine model to investigate the in vivo properties of human iPSC-RBCs. iPSC lines were produced from human peripheral blood mononuclear cells by transient expression of plasmids containing OCT4, SOX2, MYC, KLF4, and BCL-XL genes. Human iPSC-RBCs were generated in culture supplemented with human platelet lysate, and were CD34CD235a+ CD233+ CD49dlow CD71low; about 13% of iPSC-RBCs were enucleated before transfusion. Systemic administration of clodronate liposomes (CL) and cobra venom factor (CVF) to NOD scid gamma (NSG) mice markedly promoted the circulatory survival of human iPSC-RBCs following transfusion. While iPSC-RBCs progressively decreased with time, 90% of circulating iPSC-RBCs were enucleated 1 day after transfusion (CD235a+ CD233+ CD49d CD71). Surprisingly, human iPSC-RBCs reappeared in the peripheral circulation at 3 weeks after transfusion at levels more than 8-fold higher than at 1 h after transfusion. Moreover, a substantial portion of the transfused nucleated iPSC-RBCs preferentially homed to the bone marrow, and were detectable at 24 days after transfusion. These results suggest that nucleated human iPSC-derived cells that homed to the bone marrow of NSG mice retained the capability to complete differentiation into enucleated erythrocytes and egress the bone marrow into peripheral blood. The results offer a new model using human peripheral blood-derived iPSC and CL/CVF-treated NSG mice to investigate the development and circulation of human erythroid cells in vivo.

Original languageEnglish (US)
Pages (from-to)194-202
Number of pages9
JournalAmerican journal of hematology
Issue number2
StatePublished - Feb 1 2022

ASJC Scopus subject areas

  • Hematology


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