Mesothelial cell transplantation in the infarct scar induces neovascularization and improves heart function.
OBJECTIVE
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.
INSERM Unit 698, Cardiovascular Remodeling, CHU Xavier Bichat-Claude Bernard, Paris, France.
Ibrahim
I
Elmadbouh
Ying
Y
Chen
Liliane
L
Louedec
Stephane
S
Silberman
Bruno
B
Pouzet
Olivier
O
Meilhac
Jean-Baptiste
JB
Michel
D000818:Animals; D004847:Epithelial Cells / Q000637:transplantation*; D006321:Heart / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation / Q000379:methods*; D013318:Stroke Volume; D014182:Transplantation, Autologous; D020257:Ventricular Remodeling