Abstract 3978: Macrophage Subpopulations are Essential for Infarct Repair With and Without Stem Cell Therapy
Both stem cells and macrophages (MΦ) play a key role in infarct repair. However, MΦ constitute a heterogeneous population: MΦ can exhibit pro-inflammatory cytokine profiles (M1), as well as anti-inflammatory and tissue repair activity (M2). Thus, we aimed to determine the effect of stem cell transplantation on MΦ subpopulations in the infarcted myocardium.
Methods and Results Mice (Balb/C) were subjected to acute MI and randomized to bone marrow mesenchymal stem cells (MSC) or saline injection into the infarct. The number of MΦ (F4/80), M1 (CD86) and M2 (CD206) in the infarcted hearts was determined by FACS at 1, 2, 3, 4 and 7 days after MI. MSC therapy did not affect the overall number of macrophages in the infarct. However, at 3 days after MI, M2/M1 ratio was significantly higher in hearts treated with MSC transplantation, compared with controls (p=0.01). In the next experiment, MΦ depletion was induced by clodronate injection. Animals (n=57) with and without MΦ depletion were subjected to MI and allocated to MSC injection (n=15) or saline (n=42) into the infarct. Survival after MI (30 days) was significantly lower in MΦ-depleted mice, with and without stem cell therapy (p=0.02).
Conclusions Our findings suggest, for the first time, that some of the favorable effects of stem cells on the infarcted heart are related to activation of reparative macrophages (M2) in situ. Macrophages play a major role in MI repair and their depletion could cause catastrophic results, with and without stem cell therapy.