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

Autor:	Moreau T; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; 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.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Evans AL; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Vasquez L; Human Genetics, Wellcome Trust Sanger Institute, Genome Campus, Hinxton CB10 1RQ, UK., Tijssen MR; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK., Yan Y; Human Genetics, Wellcome Trust Sanger Institute, Genome Campus, Hinxton CB10 1RQ, UK., Trotter MW; 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., Howard D; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Colzani M; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Arumugam M; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Wu WH; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Dalby A; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Lampela R; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Bouet G; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Hobbs CM; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Pask DC; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Payne H; Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Ponomaryov T; Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Brill A; Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Soranzo N; Human Genetics, Wellcome Trust Sanger Institute, Genome Campus, Hinxton CB10 1RQ, UK., Ouwehand WH; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK., Pedersen RA; 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.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK., Ghevaert C; Department of Haematology, University of Cambridge and NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK.; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2016 Apr 07; Vol. 7, pp. 11208. Date of Electronic Publication: 2016 Apr 07.
DOI:	10.1038/ncomms11208
Abstrakt:	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.
Databáze:	MEDLINE
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