Development of anti-atherosclerotic tissue-engineered blood vessel by A20-regulated endothelial progenitor cells seeding decellularized vascular matrix.
To investigate whether decellularized vascular tissues and A20-regulated endothelial progenitor cells can be used for constructing a transgenic tissue-engineered blood vessel with anti-atherosclerotic vascular stenotic properties. A20 gene-transfected endothelial progenitor cells differentiated endothelial cells and smooth muscle cells attached to and migrated into the decellularized porcine vascular scaffolding in a bioreactor. The histology of the conduits revealed viable and layered tissue. Scanning electron microscopy showed confluent, homogeneous tissue surfaces. The mechanical strength of the pulsed constructs was similar to that of the human artery. In vivo, the A20 gene-transfected tissue-engineered blood vessels were transplanted into the carotid artery of a rat for 6 months. Blood vessel xenotransplantation caused hyperacute rejection; all transplanted control blood vessels were completely rejected, but A20-transfected tissue-engineered blood vessels demonstrated good flow on implantation, and remained open for 6 months postoperatively, as assessed by Doppler. The HE stain demonstrated that the vessels were patent, without evidence of stenosis or dilatation after 6 months. These results demonstrate that transgenic tissue-engineered blood vessels have long-term patency and unique anti-stenotic properties.
Zhu
Chuhong
C
Department of Anatomy, Key Lab for Biomechanics of Chongqing, Third Military Medical University, Gao Tan Yan Street, Shaping Ba District, Chongqing 400038, China. zhuch99@yahoo.com
Ying
Dajun
D
Mi
Jianhong
J
Li
Li
L
Zeng
Wen
W
Hou
Chunli
C
Sun
Jiansen
J
Yuan
Wei
W
Wen
Can
C
Zhang
Wei
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D050197:Atherosclerosis / Q000517:prevention & control*; D001808:Blood Vessels / Q000502:physiology*; D002339:Carotid Arteries / Q000637:transplantation; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology; D005109:Extracellular Matrix / Q000737:chemistry; D024022:Fibrillar Collagens / Q000737:chemistry; D018014:Gene Transfer Techniques; D006084:Graft Rejection; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*; D014162:Transfection; D014183:Transplantation, Heterologous; D014471:Umbilical Veins / Q000166:cytology; D014654:Vascular Patency
D000911:Antibodies, Monoclonal; D024022:Fibrillar Collagens