Vascular adventitia is a suitable compartment to transplant transduced vascular smooth muscle cells for ex vivo gene expression.
Vascular smooth muscle cells (VSMC) are ideal for systemic gene therapy because of their proximity to blood vessels and they have demonstrated long-term exogenous gene expression in vivo. However, the procedure generally followed to seed the transduced VSMC onto arteries denuded of endothelial cells usually induces stenosis and thrombosis, with a consequent high risk for use in humans. We demonstrate here that the vascular adventitia is a suitable place to introduce transduced VSMC and to secrete therapeutic proteins into the blood stream by a simple procedure, avoiding postoperative vascular complications. Transduced VSMC, with the retroviral vectors carrying the human growth hormone gene (hGH), were seeded into the adventitia of the rat abdominal aorta by single injection of a cell suspension. Based on the hGH and anti-hGH production in serum and on histological analysis of the removed aortas, we demonstrated hGH production over the 2-month experimental period. None of the animals used in the experiment showed stenosis, thrombosis, or other vascular or visible physiological abnormalities.
Beltrão-Braga
Patricia C B
PC
Department of Biophysics, UNIFESP-EPM, São Paulo, Brazil.
Koh
Ivan H J
IH
Silva
Maria R R
MR
Gutierrez
Paulo S
PS
Han
Sang W
SW
D016475:3T3 Cells; D000818:Animals; D001012:Aorta, Abdominal; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D019382:Human Growth Hormone / Q000097:blood / Q000235:genetics; D006801:Humans; D007700:Kinetics; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000637:transplantation*; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae; D020079:Terminal Repeat Sequences; D014162:Transfection / Q000379:methods; D015032:Zinc / Q000494:pharmacology
D018076:DNA, Complementary; D019382:Human Growth Hormone; D015032:Zinc