Induced Pluripotent Stem Cell-Derived Red Blood Cells, Megakaryocytes, and Platelets: Progress and Challenges

Human induced pluripotent stem cells (iPSCs) represent an attractive source to generate in vitro-derived red blood cells, megakaryocytes, and platelets for transfusion support. We review the progress made and challenges remaining for generating terminally differentiated red cells and platelets suitable for clinical application.

Human iPSC hematopoietic differentiation protocols primarily recapitulate the primitive stage of hematopoiesis, but a different hematopoietic progenitor that mimics the second wave of hematopoiesis has been identified that generates definitive blood cells. Coupled with strategies to improve maturation and expansion, this provides new opportunities to generate red cells and platelets that can mature, enucleate, and proliferate to clinical scale.

The major challenges of human iPSC-derived transfusion products are terminal differentiation and scalability. Despite these challenges, iPSCs offer a new source for unlimited generation of red cells and platelets with rare phenotypes for transfusion, blood bank reagents, and novel drug delivery systems.