Large-scale Production of Megakaryocytes from Human Pluripotent Stem Cells by Chemically Defined Forward Programming

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Apr 8

PMID 27052461

Citations 110

Authors

Thomas Moreau

Amanda L Evans

Louella Vasquez

Marloes R Tijssen

Ying Yan

Matthew W Trotter

Daniel Howard

Maria Colzani

Meera Arumugam

Wing Han Wu

Amanda Dalby

Riina Lampela

Guenaelle Bouet

Catherine M Hobbs

Dean C Pask

Holly Payne

Tatyana Ponomaryov

Alexander Brill

Nicole Soranzo

Willem H Ouwehand

Roger A Pedersen

Cedric Ghevaert

Affiliations

Soon will be listed here.

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.

Citing Articles

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