Abstract 4298: Adipose-Derived Stem Cell Sheet Transplantation Therapy on Swine Chronic Heart Failure Model
Introduction. Adipose-derived stem cells (ASCs) are one of the promising cell sources of the cell transplantation therapy for the damaged heart. Grafted cell death early after the transplantation is the main cause of unsatisfactory therapeutic efficacy, however, tissue engineered cell sheets with temperature-responsive cell culture dishes enable improved engraftment of transplanted cells. We previously reported ASC sheet transplantation for the myocardium repair in rat. The aim of this study was to investigate the therapeutic potency of this method on chronic myocardial ischemia in swine.
Methods and Results. We created a swine chronic heart failure model by ligating the distal portion of the left anterior descending artery (LAD) at the origin of the second diagonal artery, followed by implantation of an ameroid constrictor around the main trunk of the LAD just distal to the circumflex branch. Simultaneously, ASCs were obtained from a piece of subcutaneous adipose tissue and expanded to form ASC sheets using temperature-responsive dishes. Four weeks after the ameroid constrictor placement, we transplanted the triple-layered ASC sheets onto the border area of ischemic and infarcted myocardium (sheet group, n=7), or no sheet (control group, n=7). Just before and four weeks after the transplantation, left ventriculography (LVG) and coronary angiography (CAG) were performed for evaluation. LVG revealed significant improvement of ejection fraction in the sheet group compared to the control (47.6 ± 7.6 vs 41.4 ± 7.5 %, p<0.05). Furthermore, development of collateral vessels was only detected in the right CAG of the sheet group. The histological analysis demonstrated engrafted ASC sheets grew to form a thickened layer that included newly formed vessels.
Conclusion. ASC sheet transplantation therapy is an intriguing therapeutic method for ischemic heart failure.