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Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming
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Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming
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Journal Article
Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming
2016
Overview
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.
Platelets are blood circulating corpuscles generated from megakaryocytes that initiate wound healing. Here, Moreau
et al
. describe a way of producing large quantities of megakaryocytes from human pluripotent stem cells in the laboratory, moving us a step closer to manufacturing transfusion products.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 14/19
/ 14/28
/ 38/39
/ 42/100
/ 42/44
/ 631/80
/ Basic Helix-Loop-Helix Transcription Factors - genetics
/ Basic Helix-Loop-Helix Transcription Factors - metabolism
/ Blood Platelets - metabolism
/ GATA1 Transcription Factor - genetics
/ GATA1 Transcription Factor - metabolism
/ Green Fluorescent Proteins - genetics
/ Green Fluorescent Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - metabolism
/ Proto-Oncogene Protein c-fli-1 - genetics
/ Proto-Oncogene Protein c-fli-1 - metabolism
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Science
