A tissue-engineered stent for cell-based vascular gene transfer.
Cell-based gene transfer using a stent platform would provide a significant advantage in terms of site-specific gene expression in the vasculature. The current study presents a novel stent design that allows stable in vivo transgene expression over a 4-week period in the vasculature. A mesh-stent coated with fibronectin provided an excellent platform for adherent porcine smooth muscle cells (SMC). Autologous porcine SMC were stably transduced with a plasmid encoding green fluorescence protein (GFP), seeded at high density in the mesh-stent, and deployed in the porcine coronary artery. Stable in vivo GFP expression within the mesh-stent (5.2 x 10(5) GFP-positive cells/cm(2) mesh) was demonstrated 1 month after implantation in the porcine coronary artery by fluorescence microscopy and flow cytometry. No significant change in GFP positive cell number within the stent occurred over a 1-month period in vivo when compared to preinsertion. Angiographic and histologic analysis revealed mild neointimal proliferation and no inflammatory infiltrate in the stented segment. This study has implications for treatment of cardiovascular and other diseases where long-term cell-based delivery of transgene is a desirable therapeutic option.
Panetta
Carmelo J
CJ
Division of Cardiovascular Diseases and Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905, USA.
Miyauchi
Katsumi
K
Berry
David
D
Simari
Robert D
RD
Holmes
David R
DR
Schwartz
Robert S
RS
Caplice
Noel M
NM
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D009131:Muscle, Smooth, Vascular / Q000502:physiology / Q000637:transplantation; D010957:Plasmids; D015607:Stents; D013552:Swine; D013997:Time Factors; D023822:Tissue Engineering
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins