In vivo assessment of a tissue-engineered vascular graft combining a biodegradable elastomeric scaffold and muscle-derived stem cells in a rat model.
Limited autologous vascular graft availability and poor patency rates of synthetic grafts for bypass or replacement of small-diameter arteries remain a concern in the surgical community. These limitations could potentially be improved by a tissue engineering approach. We report here our progress in the development and in vivo testing of a stem-cell-based tissue-engineered vascular graft for arterial applications. Poly(ester urethane)urea scaffolds (length = 10 mm; inner diameter = 1.2 mm) were created by thermally induced phase separation (TIPS). Compound scaffolds were generated by reinforcing TIPS scaffolds with an outer electrospun layer of the same biomaterial (ES-TIPS). Both TIPS and ES-TIPS scaffolds were bulk-seeded with 10 x 10(6) allogeneic, LacZ-transfected, muscle-derived stem cells (MDSCs), and then placed in spinner flask culture for 48 h. Constructs were implanted as interposition grafts in the abdominal aorta of rats for 8 weeks. Angiograms and histological assessment were performed at the time of explant. Cell-seeded constructs showed a higher patency rate than the unseeded controls: 65% (ES-TIPS) and 53% (TIPS) versus 10% (acellular TIPS). TIPS scaffolds had a 50% mechanical failure rate with aneurysmal formation, whereas no dilation was observed in the hybrid scaffolds. A smooth-muscle-like layer of cells was observed near the luminal surface of the constructs that stained positive for smooth muscle alpha-actin and calponin. LacZ+ cells were shown to be engrafted in the remodeled construct. A confluent layer of von Willebrand Factor-positive cells was observed in the lumen of MDSC-seeded constructs, whereas acellular controls showed platelet and fibrin deposition. This is the first evidence that MDSCs improve patency and contribute to the remodeling of a tissue-engineered vascular graft for arterial applications.
Nieponice
Alejandro
A
Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, PA, USA.
Soletti
Lorenzo
L
Guan
Jianjun
J
Hong
Yi
Y
Gharaibeh
Burhan
B
Maul
Timothy M
TM
Huard
Johnny
J
Wagner
William R
WR
Vorp
David A
DA
D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D001672:Biocompatible Materials; D001807:Blood Vessel Prosthesis; D020724:Elastomers; D007763:Lac Operon; D008855:Microscopy, Electron, Scanning; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D011091:Polyesters; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D014162:Transfection; D014184:Transplantation, Homologous
D001672:Biocompatible Materials; D020724:Elastomers; D011091:Polyesters; C497893:poly(ester urethane)urea