Abstract 19797: Enhanced Engraftment of Mesenchymal Stem Cells With Pro-survival Factors Improves Outcome in the Infarcted Heart

Mesenchymal stem cells are under study as exemplary adult progenitor cells for repair of heart tissue injury. Many clinical studies utilizing MSCs are underway, however the ideal approach to prepare these cells in vitro, and deliver them to injury sites in vivo with maximal effectiveness is still under study. In this report, MSCs from rat bone marrow were used to examine the 1) effect of anti-apoptotic factors on the cells’ viability when challenged in vitro and 2) effect on in vivo cardiac infarct physiologic parameters. Methods: Lewis rats underwent myocardial ischemia and reperfusion by temporary ligation (45 min) of the left anterior descending coronary. The periinfarct area then received five myocardial injections with either untreated or anti-apoptotic factor treated MSCs. Animals underwent transthoracic echocardiography over 8 weeks. Results: The treated MSCs had reduced in vitro apoptosis (Figure A). The MSCs treated with anti-apoptotic factors were tested in vivo to examine if the survival of MSCs was enhanced and could improve infarct physiologic parameters. The anti-apoptotic factor treated MSCs improved the injured hearts more than untreated MSCs by echocardiographic measurements: improved ejection fraction (58.4 ± 6.5 vs. 46.6 ± 8.6 respectively, p =0.01) and greater fractional shortening (32.2 ± 4.6 vs. 24.3 ± 5.3 respectively, p =0.009). Both were better than medium alone infarct controls (Figure B). The treated MSCs were detected in the hearts in greater abundance and at later interval than the untreated MSCs. Conclusions: MSCs that were treated to resist apoptosis survived longer in vitro and in vivo, and improved heart function more than untreated MSCs. Injury recovery improved to a far greater extent than differentiation of the limited number of surviving cells could provide; this is consistent with the MSCs providing growth factors and cytokines to reduce inflammation and aid recovery of the endogenous cells in the region of injury.