Angiogenesis in tissue-engineered small intestine.
Tissue-engineered intestine offers promise as a potential novel therapy for short bowel syndrome. In this study we characterized the microvasculature and angiogenic growth factor profile of the engineered intestine. Twenty-three tissue-engineered small intestinal grafts were harvested from Lewis rat recipients 1 to 8 weeks after implantation. Architectural similarity to native bowel obtained from juvenile rats was assessed with hematoxylin and eosin-stained sections. Capillary density, measured after immunohistochemical staining for CD34, was expressed as number of capillaries per 1000 nuclei. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) tissue levels were measured by ELISA and normalized to total protein. Over the 8-week period cysts increased in volume (0.5 cm(3) at week 1 versus 12.6 cm(3) at week 8) and mass (1.30 +/- 0.29 versus 9.74 +/- 0.3 g; mean +/- SEM). Muscular and mucosal layers increased in thickness, but capillary density remained constant (82.95 +/- 4.81 capillaries per 1000 nuclei). The VEGF level was significantly higher in juvenile rat bowel than in engineered cyst (147.6 +/- 23.9 versus 42.3 +/- 3.4 pg/mg; p < 0.001). Tissue bFGF levels were also higher (315 +/- 65.48 versus 162.3 +/- 15.09 pg/mg; p < 0.05). The mechanism driving angiogenesis differs in engineered intestine and in normal bowel. VEGF and bFGF delivery may prove useful for bioengineering of intestine.
Gardner-Thorpe
James
J
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Grikscheit
Tracy C
TC
Ito
Hiromichi
H
Perez
Alexander
A
Ashley
Stanley W
SW
Vacanti
Joseph P
JP
Whang
Edward E
EE
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006085:Graft Survival / Q000502:physiology*; D007421:Intestine, Small / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering / Q000379:methods*; D019737:Transplants; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2