Abstract 3874: Age Associated Responsiveness to Allogeneic Mesenchymal Stem Cell (MSC) Transplantation After Ischemia-Reperfusion (IR) in Rats
Background It is increasingly appreciated that host factors play crucial roles in the responsiveness to cell therapy for ischemic heart disease. We tested the hypothesis that advanced age would impair cardiac repair following acute MI.
Methods Allogeneic bone marrow-derived MSC (5.0×106 cells) from a young (3 month-old) male GFP-transgenic rat or PBS were injected intramyocardially after ischemia (45 min) and reperfusion (5 min) in young and old (6 and 22 month-old, respectively) female Fisher-344 rats. Cardiac structure and function were assessed before and after cell transplantation by echocardiography. Only infarct size larger than 30% was included in this study. Hemodynamic measurements by pressure-volume conductance catheter system were performed at week 8 before sacrificing the animals.
Results In young animals, MSC therapy improved EF at week 8 (from 40.5±1.1 to 54.8±1.2%, p<0.01); however, this effect was markedly attenuated in old rats (39.1±1.1 vs. 43.3±2.9%, placebo vs. treated, same age, p=NS). Similarly, hemodynamic measurements (table⇓) showed an increase in myocardial contractility - preload-recruited-stroke-work (PRSW) in young rats (from 28.4±1.4 to 39.3±2.0; placebo vs. treated, p<0.05) but not in old rats (26.7±3.8 vs. 34.7±4.4; placebo vs. treated, p=NS). Heart rate was similar in all groups.
Conclusions Together our findings show that allogeneic MSCs improve cardiac function in young but not old rats. Accordingly, age of the recipient represents a critical factor in the ability of the host to respond to cell therapy. This finding has implications for ongoing clinical trials of this strategy.