Tissue-engineered blood vessels with endothelial nitric oxide synthase activity.
Nondegradable synthetic polymer vascular grafts used in cardiovascular surgery have shown serious shortcomings, including thrombosis, calcification, infection, and lack of growth potential. Tissue engineering of vascular grafts with autologous stem cells and biodegradable polymeric materials could solve these problems. The present study is aimed to develop a tissue-engineered vascular graft (TEVG) with functional endothelium using autologous bone marrow-derived cells (BMCs) and a hybrid biodegradable polymer scaffold. Hybrid biodegradable polymer scaffolds were fabricated from poly(lactide-co-epsilon-caprolactone) (PLCL) copolymer reinforced with poly(glycolic acid) (PGA) fibers. Canine bone marrow mononuclear cells were induced in vitro to differentiate into vascular smooth muscle cells and endothelial cells. TEVGs (internal diameter: 10 mm, length: 40 mm) were fabricated by seeding vascular cells differentiated from BMCs onto PGA/PLCL scaffolds and implanted into the abdominal aorta of bone marrow donor dogs (n = 7). Eight weeks after implantation of the TEVGs, the vascular grafts remained patent. Histological and immunohistochemical analyses of the vascular grafts retrieved at 8 weeks revealed the regeneration of endothelium and smooth muscle and the presence of collagen. Western blot analysis showed that endothelial nitric oxide synthase (eNOS) was expressed in TEVGs comparable to native abdominal aortas. This study demonstrates that vascular grafts with significant eNOS activity can be tissue-engineered with autologous BMCs and hybrid biodegradable polymer scaffolds.
Lim
Sang Hyun
SH
Department of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, Suwon 443-749, Korea.
Cho
Seung-Woo
SW
Park
Jong-Chul
JC
Jeon
Oju
O
Lim
Jae Min
JM
Kim
Sang-Soo
SS
Kim
Byung-Soo
BS
D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology; D001705:Bioprosthesis; D001807:Blood Vessel Prosthesis; D001854:Bone Marrow Cells / Q000378:metabolism*; D002454:Cell Differentiation; D004285:Dogs; D004730:Endothelium, Vascular / Q000201:enzymology*; D005786:Gene Expression Regulation; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D012038:Regeneration; D013234:Stem Cells / Q000201:enzymology*; D023822:Tissue Engineering / Q000379:methods
D011091:Polyesters; C505727:poly(epsilon-caprolactone-co-lactide); D011100:Polyglycolic Acid; D052250:Nitric Oxide Synthase Type III