title: Retrograde coronary vein infusion of cardiac explant-derived c-Kit+ cells improves function in ischemic heart failure.
abstract: BACKGROUND
  Progenitor cells isolated from cardiac explant-derived cells improve cardiac function after myocardial infarction (MI). To fully realize the therapeutic potential of these cells, it is essential to develop a safe and efficient delivery method. Therefore, the objective of this study was to determine the efficacy of our newly developed approach to retrograde coronary vein (RCV) infusion of cardiac c-Kit(+) cells in a small-animal model of congestive heart failure (CHF).
  
  
  METHODS
  Sprague-Dawley rats underwent experimental MI. After 21 days, cardiac explant-derived c-Kit(+) cells were delivered to both sham and CHF animals using RCV delivery. Vehicle-treated (serum-free medium) sham and CHF animals were used as controls. Cardiac function and heart tissues were evaluated 21 days post-transplantation.
  
  
  RESULTS
  RCV-delivered cells were retained in infarcted hearts for at least 21 days after transplantation. At 21 days post-RCV infusion, the majority of transplanted c-Kit(+)/GFP(+) cells were localized in the left ventricle. Compared with vehicle-treated CHF animals, RCV-treated rats showed a significant improvement in cardiac function. Furthermore, RCV-treated rats exhibited an increase in capillary density, a decrease in total heart collagen, and a reduction in both infarct size and cardiomyocyte hypertrophy when compared with vehicle-treated CHF rats.
  
  
  CONCLUSIONS
  Our study showed that the RCV infusion approach is an efficient technique for targeted cell delivery to the infarcted myocardium. Cardiac c-Kit(+) cells, delivered using RCV infusion ameliorated progression of heart failure, improved cardiac function and retarded myocardial remodeling in heart failure rats.
authors.affiliation: Center for Cardiovascular Research, Banner Sun Health Research Institute, Sun City, Arizona.
authors.forename: Liudmila
authors.initials: L
authors.lastname: Zakharova
authors.affiliation: Center for Cardiovascular Research, Banner Sun Health Research Institute, Sun City, Arizona.
authors.forename: Hikmet
authors.initials: H
authors.lastname: Nural-Guvener
authors.affiliation: Center for Cardiovascular Research, Banner Sun Health Research Institute, Sun City, Arizona.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Feehery
authors.affiliation: Center for Cardiovascular Research, Banner Sun Health Research Institute, Sun City, Arizona.
authors.forename: Snjezana
authors.initials: S
authors.lastname: Popovic
authors.affiliation: Center for Cardiovascular Research, Banner Sun Health Research Institute, Sun City, Arizona.
authors.forename: James
authors.initials: J
authors.lastname: Nimlos
authors.affiliation: Center for Cardiovascular Research, Banner Sun Health Research Institute, Sun City, Arizona. Electronic address: mohamed.gaballa@bannerhealth.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Gaballa
mesh_terms: D000818:Animals; D003331:Coronary Vessels; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology / Q000628:therapy; D032383:Myocytes, Cardiac / Q000637:transplantation*; D019009:Proto-Oncogene Proteins c-kit; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D020257:Ventricular Remodeling
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: cardiac stem cells; congestive heart failure; myocardial infarction; retrograde venous perfusion; stem cell transplantation