%0 Journal Article
%T Characterization and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cells
%A Ali Nsair
%A Katja Schenke-Layland
%A Ben Van Handel
%A Denis Evseenko
%A Michael Kahn
%A Peng Zhao
%A Joseph Mendelis
%A Sanaz Heydarkhan
%A Obina Awaji
%A Miriam Vottler
%A Susanne Geist
%A Jennifer Chyu
%A Nuria Gago-Lopez
%A Gay M. Crooks
%A Kathrin Plath
%A Josh Goldhaber
%A Hanna K. A. Mikkola
%A W. Robb MacLellan
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0045603
%X Background Cardiovascular progenitor cells (CPCs) have been identified within the developing mouse heart and differentiating pluripotent stem cells by intracellular transcription factors Nkx2.5 and Islet 1 (Isl1). Study of endogenous and induced pluripotent stem cell (iPSC)-derived CPCs has been limited due to the lack of specific cell surface markers to isolate them and conditions for their in vitro expansion that maintain their multipotency. Methodology/Principal Findings We sought to identify specific cell surface markers that label endogenous embryonic CPCs and validated these markers in iPSC-derived Isl1+/Nkx2.5+ CPCs. We developed conditions that allow propagation and characterization of endogenous and iPSC-derived Isl1+/Nkx2.5+ CPCs and protocols for their clonal expansion in vitro and transplantation in vivo. Transcriptome analysis of CPCs from differentiating mouse embryonic stem cells identified a panel of surface markers. Comparison of these markers as well as previously described surface markers revealed the combination of Flt1+/Flt4+ best identified and facilitated enrichment for Isl1+/Nkx2.5+ CPCs from embryonic hearts and differentiating iPSCs. Endogenous mouse and iPSC-derived Flt1+/Flt4+ CPCs differentiated into all three cardiovascular lineages in vitro. Flt1+/Flt4+ CPCs transplanted into left ventricles demonstrated robust engraftment and differentiation into mature cardiomyocytes (CMs). Conclusion/Significance The cell surface marker combination of Flt1 and Flt4 specifically identify and enrich for an endogenous and iPSC-derived Isl1+/Nkx2.5+ CPC with trilineage cardiovascular potential in vitro and robust ability for engraftment and differentiation into morphologically and electrophysiologically mature adult CMs in vivo post transplantation into adult hearts.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045603