Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue

Reza Ardehali, Shah R. Ali, Matthew A. Inlay, Oscar J. Abilez, Michael Q. Chen, Timothy A. Blauwkamp, Masayuki Yazawa, Yongquan Gong, Roeland Nusse, Micha Drukker, Irving L. Weissman

Research output: Contribution to journalArticlepeer-review

Abstract

A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown. Here, we have prospectively identified a population of hESC-derived ROR2+/CD13 +/KDR+/PDGFRα+ cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. We observed rare clusters of ROR2+ cells and diffuse expression of KDR and PDGFRα in first-trimester human fetal hearts. We then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2+/CD13+/KDR+/PDGFRα + cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, we show structural and functional integration of hESC-derived cardiovascular progenitors into human heart.

Original languageEnglish (US)
Pages (from-to)3405-3410
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number9
DOIs
StatePublished - Feb 26 2013
Externally publishedYes

Keywords

  • Clonal analysis
  • Engraftment
  • Mature cardiomyocytes
  • Stem cells
  • Surface markers

ASJC Scopus subject areas

  • General

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