Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair.
We postulated that combining cell based hVEGF165 gene delivery with cytokine-induced mobilization of bone marrow cells (BMC) may give better prognosis in an infarcted heart. Forty-eight myoabalated female C57BL/6J mice (20-25 g) received 1 x 10(6) BMC from transgenic GFP+ male mice. One month later, acute myocardial infarction (MI) model was developed by coronary artery ligation. Animals were grouped (N = 12) to receive intramyocardial injections of 10 microl DMEM without cells (group 1; group 2) or with 1x10(5) mesenchymal stem cells (MSC) over-expressing hVEGF165 (group 3; group 4). The animals received either cytokine therapy (group 2 and 4) or saline solution (group 1 and 3) for 7 days after MI. Hemodynamic data were obtained 4 weeks after MI using Millar's P-V system and cardiac tissue was harvested for immunohistological studies. We observed regeneration and extensive survival of BMC in and around the infarcted myocardium in groups 3 and 4. Blood vessel density was markedly enhanced in group 4 as compared with groups 1 and 2 in peri-infarct area. Fibrotic area was significantly reduced with improved LV-contractile function in group 2 and 4. LV-systolic and diastolic functions were well-preserved in group 4 as indicated by +dP/dt, -dP/dt and Tau (glantz). We therefore conclude that transplantation of MSC overexpressing VEGF combined with cytokine induced BMC mobilization is superior to either of the monotherapy approach for angiomyogenesis and LV-function recovery.
Wang
Yigang
Y
Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine, Ohio 45267, USA.
Haider
Husnain K
HK
Ahmad
Nauman
N
Xu
Meifeng
M
Ge
Ruowen
R
Ashraf
Muhammad
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A