Erythoid Precursors from ES and iPS Cells

Augmenting our ability to supply blood products for transfusion to critically ill patients with thrombocytopenia and anemia will fulfill great clinical needs. Thus, our current PCBC U01 project is directed toward producing platelets from human embryonic stem (ES) cells. For this ancillary study, we propose related work to expand large numbers of red blood cell (RBC) precursors from human ES and induced pluripotent stem (iPS) cells. As part of our ongoing PCBC efforts, members of the Children’s Hospital of Philadelphia (CHOP) HUB developed efficient methods to differentiate human ES cells into bipotential megakaryocyte-erythroid precursors (MEPs) for creation of platelets. Ancillary site investigators at University of Rochester (led by James Palis) have developed novel protocols to expand RBC precursors from murine ES cells. These precursors, termed extensively self-renewing erythroblasts (ESRE), multiply 1030-fold, yet retain their capacity to differentiate into mature RBCs upon manipulation of culture conditions. Now, investigators at the CHOP HUB and ancillary site will collaborate to differentiate human ES cells into ESREs and test their ability to contribute to circulating RBCs in mice. If successful, our studies will lay the groundwork for using ES/iPS cells as a source of mature RBCs or their immediate precursors for transfusion therapies. Our proposed work synergizes with ongoing CHOP PCBC-funded studies to synthesize platelets from ES cells, incorporates innovative new ES cell culture technologies developed by ancillary site investigators and addresses the overall PCBC goal to manipulate stem cell development for transplantation therapies.

Copyright ©2013 NHLBI Progenitor Cell Biology Consortium.

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