Transplantation of Sendai viral angiopoietin-1-modified mesenchymal stem cells for ischemic limb disease.
Sendai viral vector (SeV) is emerging as a promising vector for gene therapy. However, little information is available regarding the combination of SeV-mediated gene and mesenchymal stem cell (MSC) therapy in dealing with ischemic diseases. In this study, we infected SeV to the MSCs in vitro; and injected MSCs modified with SeV harboring human angiopoietin-1 gene (SeVhAng-1) into the ischemic limb of rats in vivo. We found SeV had high transductive efficiency to the MSCs. Both MSCs and SeVhAng-1-modified MSCs improved the blood flow recovery and increased the capillary density of the ischemic limb, compared with the control. However, in contrast to MSCs, SeVhAng-1-modified MSCs had a better improvement of blood flow recovery in the ischemic limb. We further found the ischemic limb injected with SeVhAng-1-modified MSCs had strong expression of p-Akt, which improved survival of MSCs injected into the ischemic limb. This indicated SeVhAng-1 modification enhanced angiogenetic effect of MSCs by both angiogenesis and cell protection. We conclude that SeVhAng-1-modified MSCs may serve as a more effective tool in dealing with ischemic limb disease.
Piao
Wenhua
W
Department of Laboratory Medicine, Ningxia People's Hospital, YinChuan, China.
Wang
Huishan
H
Inoue
Makoto
M
Hasegawa
Mamoru
M
Hamada
Hirofumi
H
Huang
Jianhua
J
D042683:Angiopoietin-1 / Q000235:genetics* / Q000627:therapeutic use*; D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D005121:Extremities / Q000098:blood supply* / Q000473:pathology; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007267:Injections; D007511:Ischemia / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow; D029082:Sendai virus / Q000235:genetics*; D016019:Survival Analysis; D014161:Transduction, Genetic
D042683:Angiopoietin-1; D051057:Proto-Oncogene Proteins c-akt