title: The development of new immunoisolatory devices possessing the ability to induce neovascularization.
abstract: The transplantation of a bioartificial pancreas has been regarded as a potential method for successful islet transplantation without any immunosuppressive agents. The subcutaneous site is a very attractive site for transplantation of a bioartificial pancreas because of its advantage of an easy operation site. Our group has been reporting that transplantation of a bioartificial pancreas to the subcutaneous site can reverse hyperglycemia in diabetic recipients. Regarding shapes of a bioartificial pancreas, it is believed that a bag form has an advantage because it is easy to prepare a large quantity. Our group previously reported successful transplantation of a bioartificial pancreas in bag form, a mesh-reinforced polyvinyl alcohol bag (MRPB), implanted in the peritoneal cavity. We also reported that the effect of subcutaneous islet transplantation can be greatly improved with prevascularization treatment. In the present study, we attempted to combine MRPB to our protocol of subcutaneous prevascularization. The main problem of this trial is that the procedure of MRPB implantation injures the prevascularized blood vessel networks. To solve this problem, we made a slight alternation in our protocol, and designed new devices on the basis of MRPB. The new devices, possessing the ability to induce neovascularization, were prepared by collagen coating on the surface of MRPB and were implanted with/without different doses of FGF-2 impregnated in gelatin microspheres. When using 5 microg of FGF-2, more blood vessels were observed on the surface of type I/IV collagen-coated MRPB compared with the original MRPB and type I collagen-coated MRPB. Quite a few blood vessels were observed either around the injection site of 50 microg of FGF-2 impregnated in gelatin microspheres alone or around the implantation site of FGF-2-free gelatin microspheres and type I collagen-coated MRPB or type I/IV collagen-coated MRPB. Here we demonstrated that the combination of both FGF-2 impregnated in gelatin microspheres and collagen-coated MRPB could give an effective system of neovascularization suitable for subcutaneous implantation of a bioartificial pancreas.
authors.affiliation: Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan, 606-8507.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sakurai
authors.forename: Akira
authors.initials: A
authors.lastname: Satake
authors.forename: Natsuki
authors.initials: N
authors.lastname: Nagata
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Gu
authors.forename: Akihito
authors.initials: A
authors.lastname: Hiura
authors.forename: Kim
authors.initials: K
authors.lastname: Doo-Hoon
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hori
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Sumi
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005780:Gelatin / Q000737:chemistry; D007150:Immunohistochemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008956:Models, Chemical; D018919:Neovascularization, Physiologic; D010179:Pancreas / Q000502:physiology*; D016035:Pancreas Transplantation; D010537:Peritoneum / Q000473:pathology; D011142:Polyvinyl Alcohol / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D016222:Fibroblast Growth Factor 2; D005780:Gelatin; D011142:Polyvinyl Alcohol; D003094:Collagen