Mesothelial cell transplantation in the infarct scar induces neovascularization and improves heart function

OBJECTIVES: Cell transplantation and associated neovascularization in vivo may be beneficial in ischemic disease. We hypothesized that transplanted mesothelial cells (MCs) could improve neovascularization in the post-myocardial infarct scar in rats. METHODS: Myocardial infarction was created by left coronary artery ligation in Lewis rats. After 3 weeks, surviving rats with left ventricular (LV) ejection fraction (EF) <50% were randomized into 2 groups which received, via injection into the infarct scar, either syngeneic rat peritoneal MCs (transplanted group) or vehicle alone (control group). Rats were followed-up echocardiographically for 4 weeks. Before transplantation, cells were transfected in vitro or labeled by a fluorescent dye for subsequent tracking in vivo. Transplanted cells and neovascularization were assessed histologically in the infarct scar by immunostaining or intravenous FITC-dextran injection prior to sacrifice, from 1 to 30 days post-transplantation. RESULTS: Among other pro-angiogenic chemokines, cultured MCs released stromal cell-derived factor (SDF-1alpha) (15.9 +/- 1.8 microg/mg protein) in vitro. At 1 month, some transplanted MCs were visualized (surviving or proliferating) in the LV scar and were incorporated in new vessels. The transplanted rats presented an increased vascular density in the scar, improved LV-EF (44.0 +/- 8.6% vs. 24.0 +/- 4.5%, p < 0.01) with decreased LV end-diastolic diameter (9.6 +/- 0.6 vs. 11.1 +/- 0.6 mm, p < 0.01) and volume (0.47 +/- 0.1 vs. 0.63+/-0.1 ml, p < 0.01) vs. controls. One week post-transplantation, higher levels of SDF-1alpha were extracted from LV peri-infarct tissue (32.3 +/- 5.8 vs. 22.6 +/- 3.1 pg/mg protein in controls, p < 0.01). CONCLUSIONS: Since autologous MCs can be obtained easily and cultured in large quantities, MC transplantation may represent a new angiogenic strategy in the prevention of ischemic remodeling.