title: Maintenance of neovascularization at the implantation site of an artificial device by bFGF and endothelial cell transplant.
abstract: Development of a subcutaneously implantable bioartificial pancreas (BAP) with immunoisolatory function could have a great impact on the treatment of diabetes mellitus. We have developed an implantable BAP device with an ethylene vinyl alcohol (EVAL) membrane. In the present study, we used basic fibroblast growth factors (bFGF), which was incorporated in a carrier for sustained release, in order to induce neovascularization when the device was implanted subcutaneously. To maintain the vasculature thus formed, a cell infusion port was attached to the BAP device, through which the device was filled with human liver vascular endothelial cell line TMNK-1, and the vasculature could be adequately maintained. Mice were divided into the following three groups. In group 1, a bFGF-free BAP device was implanted subcutaneously. In group 2, a sustained-release bFGF-impregnated BAP device was implanted. In group 3, a sustained-release bFGF-impregnated BAP device was implanted, and 3 x 10(6) TMNK-1 cells were infused into the implanted device every week. Neovascularization induced in the subcutaneous tissue around the implanted BAP device was macroscopically examined and histologically evaluated. In addition, the tissue blood flow was measured using a laser blood flow meter. In mice in group 3, neovascularization was significantly induced and maintained until week 8 postimplantation. It was confirmed by scanning electron microscopy that infused TMNK-1 cells adhered to the inner polyethylene surface of the device. It was demonstrated that the use of bFGF and vascular endothelial TMNK-1 cells induced and maintained adequate vasculature and tissue blood flow surrounding the implantable bag-type BAP device. We believe that the present study will contribute to BAP development for the treatment of diabetes.
authors.affiliation: Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miki
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Rivas-Carrillo
authors.forename: Nalu
authors.initials: N
authors.lastname: Navarro-Alvarez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soto-Gutierrez
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Tanaka
authors.forename: Michiki
authors.initials: M
authors.lastname: Narushima
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Teru
authors.initials: T
authors.lastname: Okitsu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Naoya
authors.initials: N
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000648:ultrastructure; D002448:Cell Adhesion; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology* / Q000637:transplantation / Q000648:ultrastructure; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019397:Pancreas, Artificial; D014183:Transplantation, Heterologous
chemical_list: D016222:Fibroblast Growth Factor 2