Intracoronary Infusion of Allogeneic Mesenchymal Precursor Cells Directly Following Experimental Acute Myocardial Infarction Reduces Infarct Size, Abrogates Adverse Remodeling and Improves Cardiac Function
Rationale: Mesenchymal precursor cells (MPC) are a specific stro3+ sub population of mesenchymal stem cells (MSC) isolated from bone marrow. MPC exert extensive cardioprotective effects, and are considered to be immune-privileged.
Objective: This study assessed the safety, feasibility and efficacy of intracoronary delivery of allogeneic MPC directly following acute myocardial infarction (AMI) in sheep.
Methods and Results: Initially, intracoronary delivery conditions were optimized in 20 sheep. These conditions were applied in a randomized study of 68 sheep with an anterior AMI. Coronary flow was monitored during MPC infusion and cardiac function was assessed using invasive hemodynamics and echocardiography at baseline and during 8 week follow up. Coronary flow remained within TIMI III definitions in all sheep during MPC infusion. Global LVEF as measured by PV-loop analysis deteriorated in controls to 40.7±2.6% after eight weeks. In contrast, MPC treatment improved cardiac function to 52.8±0.7%. Echocardiography revealed significant improvement of both global and regional cardiac function. Infarct size decreased by 40% in treated sheep, whereas infarct and border zone thickness were enhanced. LV adverse remodeling was abrogated by MPC therapy, resulting in a marked reduction of LV volumes. Blood vessel density increased by >50% in the infarct and border areas. Compensatory cardiomyocyte hypertrophy was reduced in border and remote segments, accompanied by reduced collagen deposition and apoptosis. No micro-infarctions in remote myocardial segments or histological abnormalities in unrelated organs were found.
Conclusions: Intracoronary infusion of allogeneic MPC is safe, feasible and markedly effective in a large animal model of AMI.
- mesenchymal precursor cell
- cell therapy
- acute myocardial infarction
- mesenchymal stem cell
- cell transplantation
- primary percutaneous coronary intervention
- Received December 10, 2012.
- Revision received May 6, 2013.
- Accepted May 8, 2013.