title: Reduced collagen deposition in infarcted myocardium facilitates induced pluripotent stem cell engraftment and angiomyogenesis for improvement of left ventricular function.
abstract: OBJECTIVE
  The purpose of this study was to assess the effect of scar tissue composition on engraftment of progenitor cells into infarcted myocardium.
  
  
  BACKGROUND
  Scar tissue formation after myocardial infarction creates a barrier that severely compromises tissue regeneration, limiting potential functional recovery.
  
  
  METHODS
  In vitro: A tricell patch (Tri-P) was created from peritoneum seeded and cultured with induced pluripotent stem cell-derived cardiomyocytes, endothelial cells, and mouse embryonic fibroblasts. The expression of fibrosis-related molecules from mouse embryonic fibroblasts and infarcted heart was measured by Western blot and quantitative reverse transcriptase polymerase chain reaction. In vivo: A Tri-P was affixed over the entire infarcted area 7 days after myocardial infarction in mice overexpressing adenylyl cyclase 6 (AC6). Engraftment efficiency of progenitor cells in hearts of AC6 mice was compared with that of control wild-type (WT) mice using a combination of in vivo bioluminescence imaging, post-mortem ex vivo tissue analysis, and the number of green fluorescent protein-positive cells. Echocardiography of left ventricular (LV) function was performed weekly. Hearts were harvested for analysis 4 weeks after Tri-P application. Mouse embryonic fibroblasts were stimulated with forskolin before an anoxia/reoxygenation protocol. Fibrosis-related molecules were analyzed.
  
  
  RESULTS
  In AC6 mice, infarcted hearts treated with Tri-P showed significantly higher bioluminescence imaging intensity and numbers of green fluorescent protein-positive cells than in WT mice. LV function improved progressively in AC6 mice from weeks 2 to 4 and was associated with reduced LV fibrosis.
  
  
  CONCLUSIONS
  Application of a Tri-P in AC6 mice resulted in significantly higher induced pluripotent stem cell engraftment accompanied by angiomyogenesis in the infarcted area and improvement in LV function.
authors: Liuhua Qiao Hospital, Guangzhou, Guangdong, China.
authors: Bo
authors: B
authors: Dai
authors: Wei
authors: W
authors: Huang
authors: Meifeng
authors: M
authors: Xu
authors: Ronald W
authors: RW
authors: Millard
authors: Mei Hua
authors: MH
authors: Gao
authors: H Kirk
authors: HK
authors: Hammond
authors: Donald R
authors: DR
authors: Menick
authors: Muhammad
authors: M
authors: Ashraf
authors: Yigang
authors: Y
authors: Wang
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D002921:Cicatrix / Q000503:physiopathology*; D003094:Collagen / Q000096:biosynthesis*; D004452:Echocardiography; D005355:Fibrosis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008163:Luminescent Measurements; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D039904:Pluripotent Stem Cells / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D012038:Regeneration; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D003094:Collagen; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6