Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.
Nat Commun
; 7: 11208, 2016 Apr 07.
Article
in En
| MEDLINE
| ID: mdl-27052461
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.
Full text:
1
Database:
MEDLINE
Main subject:
Megakaryocytes
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Proto-Oncogene Proteins
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Pluripotent Stem Cells
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Basic Helix-Loop-Helix Transcription Factors
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GATA1 Transcription Factor
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Proto-Oncogene Protein c-fli-1
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Cellular Reprogramming
Limits:
Humans
Language:
En
Year:
2016
Type:
Article