Expansion and patterning of cardiovascular progenitors derived from human pluripotent stem cells

Matthew J. Birket, Marcelo C. Ribeiro, Arie O. Verkerk, Dorien Ward, Ana Rita Leitoguinho, Sabine C. Den Hartogh, Valeria V. Orlova, Harsha D. Devalla, Verena Schwach, Milena Bellin, Robert Passier, Christine L. Mummery*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

114 Citations (Scopus)

Abstract

The inability of multipotent cardiovascular progenitor cells (CPCs) to undergo multiple divisions in culture has precluded stable expansion of precursors of cardiomyocytes and vascular cells. This contrasts with neural progenitors, which can be expanded robustly and are a renewable source of their derivatives. Here we use human pluripotent stem cells bearing a cardiac lineage reporter to show that regulated MYC expression enables robust expansion of CPCs with insulin-like growth factor-1 (IGF-1) and a hedgehog pathway agonist. The CPCs can be patterned with morphogens, recreating features of heart field assignment, and controllably differentiated to relatively pure populations of pacemaker-like or ventricular-like cardiomyocytes. The cells are clonogenic and can be expanded for >40 population doublings while retaining the ability to differentiate into cardiomyocytes and vascular cells. Access to CPCs will allow precise recreation of elements of heart development in vitro and facilitate investigation of the molecular basis of cardiac fate determination. This technology is applicable for cardiac disease modeling, toxicology studies and tissue engineering.

Original languageEnglish
Pages (from-to)970-979
Number of pages10
JournalNature biotechnology
Volume33
Issue number9
DOIs
Publication statusPublished - 10 Sep 2015
Externally publishedYes

Fingerprint Dive into the research topics of 'Expansion and patterning of cardiovascular progenitors derived from human pluripotent stem cells'. Together they form a unique fingerprint.

Cite this