title: Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.
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.
authors: Division of Cardiology, Department of Internal Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA 90095, USA. rardehali@mednet.ucla.edu
authors: Reza
authors: R
authors: Ardehali
authors: Shah R
authors: SR
authors: Ali
authors: Matthew A
authors: MA
authors: Inlay
authors: Oscar J
authors: OJ
authors: Abilez
authors: Michael Q
authors: MQ
authors: Chen
authors: Timothy A
authors: TA
authors: Blauwkamp
authors: Masayuki
authors: M
authors: Yazawa
authors: Yongquan
authors: Y
authors: Gong
authors: Roeland
authors: R
authors: Nusse
authors: Micha
authors: M
authors: Drukker
authors: Irving L
authors: IL
authors: Weissman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005333:Fetus / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D054240:Primitive Streak / Q000166:cytology; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D014022:Tissue Survival; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2
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