title: Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.
abstract: BACKGROUND
  Endogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI). However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs) have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear.
  
  
  RESULTS
  Using "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+)CD45(-) cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1) in Sca-1(+)CD45(-) cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+)CD45(-) cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts.
  
  
  CONCLUSIONS
  These studies demonstrate that cloned Sca-1(+)CD45(-) cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+)) precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.
authors.affiliation: Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.forename: Andrew
authors.initials: A
authors.lastname: Boyle
authors.forename: Henry
authors.initials: H
authors.lastname: Shih
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sievers
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Megha
authors.initials: M
authors.lastname: Prasad
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: William
authors.initials: W
authors.lastname: Grossman
authors.forename: Harold S
authors.initials: HS
authors.lastname: Bernstein
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D017209:Apoptosis; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D006321:Heart / Q000503:physiopathology; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; D060850:LIM-Homeodomain Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse