Dataset Information

Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells.

ABSTRACT:

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.

SUBMITTER: Nsair A

PROVIDER: S-EPMC3467279 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells.

Nsair Ali A Schenke-Layland Katja K Van Handel Ben B Evseenko Denis D Kahn Michael M Zhao Peng P Mendelis Joseph J Heydarkhan Sanaz S Awaji Obina O Vottler Miriam M Geist Susanne S Chyu Jennifer J Gago-Lopez Nuria N Crooks Gay M GM Plath Kathrin K Goldhaber Josh J Mikkola Hanna K A HK MacLellan W Robb WR

PloS one 20121009 10

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>We sou ...[more]

PMID: 23056209

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Dataset Information

Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells.

Background

Methodology/principal findings

Conclusion/significance

Publications

Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells.

Similar Datasets

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