title: Myocardial Reparative Properties of Cardiac Mesenchymal Cells Isolated on the Basis of Adherence.
abstract: BACKGROUND
  The authors previously reported that the c-kit-positive (c-kitPOS) cells isolated from slowly adhering (SA) but not from rapidly adhering (RA) fractions of cardiac mesenchymal cells (CMCs) are effective in preserving left ventricular (LV) function after myocardial infarction (MI).
  
  
  OBJECTIVE
  This study evaluated whether adherence to plastic alone, without c-kit sorting, was sufficient to isolate reparative CMCs.
  
  
  METHODS
  RA and SA CMCs were isolated from mouse hearts, expanded in vitro, characterized, and evaluated for therapeutic efficacy in mice subjected to MI.
  
  
  RESULTS
  Morphological and phenotypic analysis revealed that murine RA and SA CMCs are indistinguishable; nevertheless, transcriptome analysis showed that they possess fundamentally different gene expression profiles related to factors that regulate post-MI LV remodeling and repair. A similar population of SA CMCs was isolated from porcine endomyocardial biopsy samples. In mice given CMCs 2 days after MI, LV ejection fraction 28 days later was significantly increased in the SA CMC group (31.2 ± 1.0% vs. 24.7 ± 2.2% in vehicle-treated mice; p < 0.05) but not in the RA CMC group (24.1 ± 1.2%). Histological analysis showed reduced collagen deposition in the noninfarcted region in mice given SA CMCs (7.6 ± 1.5% vs. 14.5 ± 2.8% in vehicle-treated mice; p < 0.05) but not RA CMCs (11.7 ± 1.7%), which was associated with reduced infiltration of inflammatory cells (14.1 ± 1.6% vs. 21.3 ± 1.5% of total cells in vehicle and 19.3 ± 1.8% in RA CMCs; p < 0.05). Engraftment of SA CMCs was negligible, which implies a paracrine mechanism of action.
  
  
  CONCLUSIONS
  We identified a novel population of c-kit-negative reparative cardiac cells (SA CMCs) that can be isolated with a simple method based on adherence to plastic. SA CMCs exhibited robust reparative properties and offered numerous advantages, appearing to be more suitable than c-kitPOScardiac progenitor cells for widespread clinical therapeutic application.
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky; Diabetes and Obesity Center, University of Louisville School of Medicine, Louisville, Kentucky. Electronic address: m0wyso01@louisville.edu.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wysoczynski
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Moore
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Muthusamy
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Qianhong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Marjan
authors.initials: M
authors.lastname: Nasr
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Nong
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Wu
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Tomlin
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Gregory
authors.initials: G
authors.lastname: Hunt
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Gumpert
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Book
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Abdur
authors.initials: A
authors.lastname: Khan
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Xian-Liang
authors.initials: XL
authors.lastname: Tang
authors.affiliation: Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, Kentucky; Diabetes and Obesity Center, University of Louisville School of Medicine, Louisville, Kentucky. Electronic address: rbolli@louisville.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000166:cytology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012038:Regeneration; D013552:Swine
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: fibrosis; inflammation; ischemic cardiomyopathy; myocardial infarction; repair