title: Sca-1+ cardiac progenitor cell therapy with cells overexpressing integrin-linked kinase improves cardiac function after myocardial infarction.
abstract: BACKGROUND
  This study was to investigate the effect of integrin-linked kinase (ILK) on the transplantation efficiency of stem cell antigen-1-positive cardiac progenitor cells (Sca-1 CPCs) in a mouse myocardial infarction (MI) model.
  
  
  METHODS
  Sca-1 CPCs were isolated from C57/BL6 mice heart tissues and genetically modified with adenovirus vector containing green fluorescent protein (GFP)/ILK or GFP. Cell viability, migration, DNA synthesis, proliferation, and apoptosis were assessed in vitro. Immediately after MI, treated animals received 5×10 GFP-CPC or ILK-CPC transplantation into the peri-infarct myocardium. Cardiac function, exercise ability, cardiac morphology, angiogenesis, cardiomyocyte apoptosis, as well as ILK-related protein expression were measured. Acute and long-term cell survival after cell transplantation was assessed.
  
  
  RESULTS
  Overexpression of ILK increased the viability, migration, DNA synthesis, proliferation, and survival of Sca-1 CPCs in vitro. Protein expression of phosphorylated Akt and cyclin D1 were up-regulated. In our in vivo experiment, more transplanted cells were found in the peri-infarct myocardium in ILK-CPC group 3 days after cell transplantation, but there was no difference between the two groups 4 weeks later. ILK-CPC group showed reduced infarct size 7 days after cell transplantation. Long-term observation showed improved cardiac function indicated by higher percent fractional shortening and lower left ventricular end systolic diameter/left ventricular end diastolic diameter, better exercise ability, increased angiogenesis, decreased fibrosis and apoptosis, as well as up-regulation of ILK, Cdc42, and Aurora B protein expression in ILK-CPC group 4 weeks after cell transplantation.
  
  
  CONCLUSIONS
  ILK-overexpressed Sca-1 CPCs showed improved therapeutic efficacy in MI.
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ling
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
authors.forename: Rong
authors.initials: R
authors.lastname: Gu
authors.forename: Chunying
authors.initials: C
authors.lastname: Jiang
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Lina
authors.initials: L
authors.lastname: Kang
authors.forename: Albert
authors.initials: A
authors.lastname: Ferro
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis*; D017209:Apoptosis; D001835:Body Weight; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000637:transplantation*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D033581:Stem Cell Transplantation; D000099200:Scaffold Protein ILK
chemical_list: D000950:Antigens, Ly; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C074650:Ly6a protein, mouse