Similar effect of autologous and allogeneic cell therapy for ischemic heart disease: results from a meta-analysis of large animal studies

Abstract

Introduction: In regenerative therapy for ischemic heart disease use of both autologous and allogeneic stem cells have been investigated. An important drawback of autologous cell therapy is the restricted availability, especially in the acute setting. Besides, aging and exposure to risk factors could impair the potential of autologous cells. Allogeneic cell therapy enables pre-operative production of potent cell lines, immediate availability and would allow off the shelf therapy. However, allogeneic therapy may be hampered by the risk of graft rejection, the necessity of immune suppression or even HLA matching. We performed a meta-analysis of pre-clinical data of cell therapy for ischemic heart disease to investigate whether allogeneic and autologous cell therapy results in the same effect size. Methods: A systematic search was performed in PubMed and EMBASE in order to identify publications of controlled pre-clinical trials of unmodified stem cell therapy for acute and chronic myocardial ischemia in large animal models, published untill January 2013. We used a raw difference in mean meta-analysis to summarize data for left ventricular ejection fraction (LVEF) at follow up in control and treated animals. For left ventricular end systolic volume (ESV) and left ventricular end diastolic volume (EDV), a standardized difference in mean analysis was performed. A meta-regression analysis for cell source (autologous and allogeneic), type of ischemia (permanent occlusion and ischemia/reperfusion), cell type and other clinical relevant aspects and quality aspects was conducted as well. Results: We identified 82 studies, from which data of 1415 animals were included. The meta-analysis showed a significantly difference in mean LVEF in cell treated animals compared to control animals (8.3%, SE 0.6, p <0.001). This difference in LVEF can be explained by a significant difference in EDV. There is no significant difference in mean ESV between groups. Meta-regression analysis suggested that the improvement in LVEF was greater in permanent occlusion (9.8% SE 0.8 n=786) compared with ischemia/reperfusion models (6.2% SE 1.2 n=629 p=0.004). Allogeneic (n=331) and autologous (n=981) cell therapy results in a similar difference in mean LVEF (7.3% SE 1.5 vs. 8.8% SE 0.7 respectively, p=0.3). Conclusion: Cell therapy leads to a significant improvement in LVEF of 8.3% in large animal myocardial ischemia models, compared to control. Importantly, no difference in effect size was noted between allogeneic and autologous cell therapy. These results are important in view of practical issues for future clinical trials.