Sustained therapeutic perfusion outside transplanted sites in chronic myocardial infarction after stem cell transplantation

Abstract

This study aimed at comparing long-term variations in the perfusion of chronic myocardial infarction (MI) areas after local injections of autologous bone marrow stem cells (BMSCs). 14 coronary ligated rats with transmural chronic MI (4 months) were used: a control group (n = 7) versus a treated group (n = 7) in which (111)In labeled-BMSCs were directly engrafted on MI areas. By using (111)In/(99m)Tc SPECT and Sestamibi gated-SPECT,. left ventricle perfusion and function were monitored in all animals by serial (99m)Tc-Sestamibi pinhole gated-SPECT over a period of 6 months. Post-therapeutic myocardial perfusion improved as early as 48 h following injection in the 2 groups. This benefice was sustained during the 6-month follow-up in the non-engrafted MI-areas from treated rats (at 6-months: +10 ± 5 %), whereas the engrafted ones, as well as the MI areas from control rats, exhibited progressive deterioration over time (at 6-months: -9 ± 10 % and -5 ± 3 %, respectively). Perfusion enhancement of the chronic MI areas treated by BMSCs transplantation is: (1) marked in the following days, presumably because of an unspecific inflammatory reaction, and (2) sustained over the long term but only outside the sites of cell engraftment, suggesting a distant paracrine effect of transplanted cells.