Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27052461.
- Also identified by DOI 10.1038/ncomms11208 and PMC identifier 4829662.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Basic Helix-Loop-Helix Proteins
- Cellular Reprogramming
- GATA1 Transcription Factor
- Megakaryocytes
- Pluripotent Stem Cells
- Proto-Oncogene Protein c-fli-1
- Proto-Oncogene Proteins