Maintenance of neovascularization at the implantation site of an artificial device by bFGF and endothelial cell transplant

Atsushi Miki, Jorge D. Rivas-Carrillo, Nalu Navarro-Alvarez, Alejandro Soto-Gutierrez, Yong Chen, Kimiaki Tanaka, Michiki Narushima, Yasuhiko Tabata, Teru Okitsu, Hirofumi Noguchi, Shinichi Matsumoto, Noriaki Tanaka, Naoya Kobayashi

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17 Scopus citations

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 × 106 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.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalCell Transplantation
Volume15
Issue number10
DOIs
StatePublished - Dec 1 2006

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Keywords

  • Basic fibroblast growth factor
  • Bioartificial pancreas
  • Human vascular endothelial cells
  • Neovascularization

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

Miki, A., Rivas-Carrillo, J. D., Navarro-Alvarez, N., Soto-Gutierrez, A., Chen, Y., Tanaka, K., Narushima, M., Tabata, Y., Okitsu, T., Noguchi, H., Matsumoto, S., Tanaka, N., & Kobayashi, N. (2006). Maintenance of neovascularization at the implantation site of an artificial device by bFGF and endothelial cell transplant. Cell Transplantation, 15(10), 893-901. https://doi.org/10.3727/000000006783981378