Enhanced IGF-1 expression improves smooth muscle cell engraftment after cell transplantation.
The functional benefit of cell transplantation after a myocardial infarction is diminished by early cell losses. IGF-1 enhances cell proliferation and survival. We hypothesized that IGF-1-transfected smooth muscle cells (SMCs) would enhance cell survival and improve engraftment after cell transplantation. The IGF-1 gene was transfected into male SMCs and compared with SMCs transfected with a plasmid vector (vector control) and nontransfected SMCs (cell control). IGF-1 mRNA (n=10/group) and protein levels (n=6/group) were higher (P <0.05 for all groups) at 3, 7, and 14 days compared with controls. VEGF was also increased in parallel to enhanced IGF-1 expression. IGF-1-transfected cells demonstrated greater cell proliferation, stimulated angiogenesis, and decreased caspase-3 activity after simulated ischemia and reperfusion (P <0.05 for all groups compared with vector or cell controls). A uniform left ventricular injury was produced in female rats using a cryoprobe. Three weeks later, 2 x 10(6) cells from three groups were implanted into the scar. One week later, IGF-1-transfected SMCs had increased myocardial IGF-1 and VEGF levels, increased Bcl2 expression, limited cell apoptosis, and enhanced vessel formation in the myocardial scar compared with the two control groups (P <0.05 for all groups). The proportion of SMCs surviving in the implanted region was greater (P <0.05) in the IGF-1-transfected group than in the vector or cell controls. Gene enhancement with IGF-1 improved donor cell proliferation, survival, and engraftment after cell transplantation, perhaps mediated by enhanced angiogenesis and reduced apoptosis.
Toronto General Hospital, NU 1-115A, 200 Elizabeth St., Toronto, Ontario, Canada M5G 2C4.
Tian-Biao
TB
Liu
Paul W M
PW
Fedak
Richard D
RD
Weisel
Tamotsu
T
Yasuda
Gholam
G
Kiani
Donald A G
DA
Mickle
Zhi-Qiang
ZQ
Jia
Ren-Ke
RK
Li
D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D015870:Gene Expression; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D051381:Rats; D011917:Rats, Inbred Lew; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I