Reduced collagen deposition in infarcted myocardium facilitates induced pluripotent stem cell engraftment and angiomyogenesis for improvement of left ventricular function

Bo Dai, Wei Huang, Meifeng Xu, Ronald W. Millard, Mei Hua Gao, H. Kirk Hammond, Donald R. Menick, Muhammad Ashraf, Yigang Wang

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Objectives: 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 cellderived 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 proteinpositive 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 proteinpositive 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.

Original languageEnglish (US)
Pages (from-to)2118-2127
Number of pages10
JournalJournal of the American College of Cardiology
Volume58
Issue number20
DOIs
StatePublished - Nov 8 2011
Externally publishedYes

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Keywords

  • adenylyl cyclases
  • angiomyogenesis
  • induced pluripotent stem cell engraftment
  • myocardial infarction
  • tricell patch

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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