Similar effect of autologous and allogeneic cell therapy for ischemic heart disease : Systematic review and meta-analysis of large animal studies

Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells have been investigated. Autologous cell can be applied without immunosuppression but availability is restricted and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables pre-operative production of potent cell lines and immediate availability of cell products, allowing 9off the shelf9 therapy. It is unknown which cell source is preferred with regard to improving cardiac function. Objective: We performed a meta-analysis of pre-clinical data of cell therapy for ischemic heart disease. Methods and Results: We conducted a systematic literature search to identify publications describing controlled pre-clinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction (LVEF) in treated compared to control animals (8.3%, 95% CI 7.1 - 9.5, p <0.001). Meta-regression revealed a similar difference in LVEF in autologous (8.8% 95% CI 7.3 - 10.3 n= 981) and allogeneic (7.3% 95% CI 4.4 - 10.2 n= 331) (p= 0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in LVEF in large animal models of myocardial ischemia, compared to placebo. These results are important for the design of future clinical trials.