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Nat Commun. 2016 Apr 7;7:11208. doi: 10.1038/ncomms11208.

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

Author information

1
Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.
2
The Anne McLaren Laboratory, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Surgery, University of Cambridge, West Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
3
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK.
4
Human Genetics, Wellcome Trust Sanger Institute, Genome Campus, Hinxton CB10 1RQ, UK.
5
Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Abstract

The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.

PMID:
27052461
PMCID:
PMC4829662
DOI:
10.1038/ncomms11208
[Indexed for MEDLINE]
Free PMC Article

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