Author + information
- Received March 16, 2011
- Revision received June 23, 2011
- Accepted June 27, 2011
- Published online November 8, 2011.
- Bo Dai, MD, PhD⁎,†,
- Wei Huang, MD, PhD†,
- Meifeng Xu, MD, PhD†,
- Ronald W. Millard, PhD‡,
- Mei Hua Gao, PhD§,
- H. Kirk Hammond, PhD§,
- Donald R. Menick, PhD∥,
- Muhammad Ashraf, PhD† and
- Yigang Wang, MD, PhD†,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Yigang Wang, Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0529
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 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.
- adenylyl cyclases
- induced pluripotent stem cell engraftment
- myocardial infarction
- tricell patch
This work was funded by National Institutes of Health grantsHL089824, HL110740, and HL081859 (to Dr. Wang); HL-080686 and R37HL-074272 (to Dr. Ashraf).
All authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Dai and Huang contributed equally to this work.
- Received March 16, 2011.
- Revision received June 23, 2011.
- Accepted June 27, 2011.
- American College of Cardiology Foundation