title: Autologous c-Kit+ Mesenchymal Stem Cell Injections Provide Superior Therapeutic Benefit as Compared to c-Kit+ Cardiac-Derived Stem Cells in a Feline Model of Isoproterenol-Induced Cardiomyopathy.
abstract: BACKGROUND
  Cardiac- (CSC) and mesenchymal-derived (MSC) CD117+ isolated stem cells improve cardiac function after injury. However, no study has compared the therapeutic benefit of these cells when used autologously.
  
  
  METHODS
  MSCs and CSCs were isolated on day 0. Cardiomyopathy was induced (day 28) by infusion of L-isoproterenol (1,100 ug/kg/hour) from Alzet minipumps for 10 days. Bromodeoxyuridine (BrdU) was infused via minipumps (50 mg/mL) to identify proliferative cells during the injury phase. Following injury (day 38), autologous CSC (n = 7) and MSC (n = 4) were delivered by intracoronary injection. These animals were compared to those receiving sham injections by echocardiography, invasive hemodynamics, and immunohistochemistry.
  
  
  RESULTS
  Fractional shortening improved with CSC (26.9 ± 1.1% vs. 16.1 ± 0.2%, p = 0.01) and MSC (25.1 ± 0.2% vs. 12.1 ± 0.5%, p = 0.01) as compared to shams. MSC were superior to CSC in improving left ventricle end-diastolic (LVED) volume (37.7 ± 3.1% vs. 19.9 ± 9.4%, p = 0.03) and ejection fraction (27.7 ± 0.1% vs. 19.9 ± 0.4%, p = 0.02). LVED pressure was less in MSC (6.3 ± 1.3 mmHg) as compared to CSC (9.3 ± 0.7 mmHg) and sham (13.3 ± 0.7); p = 0.01. LV BrdU+ myocytes were higher in MSC (0.17 ± 0.03%) than CSC (0.09 ± 0.01%) and sham (0.06 ± 01%); p < 0.001.
  
  
  CONCLUSIONS
  Both CD117+ isolated CSC and MSC therapy improve cardiac function and attenuate pathological remodeling. However, MSC appear to confer additional benefit.
authors: Temple University Hospital, Department of Surgery, Philadelphia, Pennsylvania, USA.|Temple University School of Medicine, Cardiovascular Research Center, Philadelphia, Pennsylvania, USA.
authors: Sharven
authors: S
authors: Taghavi
authors: Temple University School of Medicine, Cardiovascular Research Center, Philadelphia, Pennsylvania, USA.
authors: Thomas E
authors: TE
authors: Sharp
authors: Temple University School of Medicine, Cardiovascular Research Center, Philadelphia, Pennsylvania, USA.
authors: Jason M
authors: JM
authors: Duran
authors: Temple University School of Medicine, Cardiovascular Research Center, Philadelphia, Pennsylvania, USA.
authors: Catherine A
authors: CA
authors: Makarewich
authors: Temple University School of Medicine, Cardiovascular Research Center, Philadelphia, Pennsylvania, USA.
authors: Remus M
authors: RM
authors: Berretta
authors: Temple University School of Medicine, Cardiovascular Research Center, Philadelphia, Pennsylvania, USA.
authors: Tim
authors: T
authors: Starosta
authors: Temple University School of Medicine, Cardiovascular Research Center, Philadelphia, Pennsylvania, USA.
authors: Hajime
authors: H
authors: Kubo
authors: Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Mary
authors: M
authors: Barbe
authors: Temple University School of Medicine, Cardiovascular Research Center, Philadelphia, Pennsylvania, USA.
authors: Steven R
authors: SR
authors: Houser
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002415:Cats; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005355:Fibrosis; D007545:Isoproterenol; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D020127:Recovery of Function; D012038:Regeneration; D013318:Stroke Volume; D013997:Time Factors; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D019009:Proto-Oncogene Proteins c-kit; D007545:Isoproterenol
keywords: cardiomyopathy; cardiovascular diseases; heart failure