Amelioration of diabetes in mice after single-donor islet transplantation using the controlled release of gelatinized FGF-2.
Fibroblast growth factor (FGF)-2 has been recognized to be a key element involved in angiogenesis and a putative factor involved in stem cell-mediated islet regeneration. However, the usefulness of FGF-2 in an islet transplantation setting has not yet been explored. We therefore evaluated the effect of FGF-2 on both islet culture and islet transplantation. Isolated islets were cultured in the presence of 100 ng/ml FGF-2 for a week and then the glucose-responding insulin secretion and insulin contents were measured. Gelatinized FGF-2 (100 ng), which allowed the controlled release of FGF-2, was used for islet transplantation of streptozotocin-induced diabetic mice. Islets (150 IEQ), obtained from a single donor, mixed with gelatinized FGF-2, were transplanted into the subrenal capsule of the mice and the animals were observed for 30 days. Revascularization around the islet grafts was examined. The blood glucose levels were measured and the intraperitoneal glucose tolerance test (IPGTT) was performed. The supplementation of FGF-2 maintained proper insulin secretion and insulin contents in an in vitro culture. The use of gelatinized FGF-2 facilitated revascularization and favorable islet engraftment, thus resulting in an amelioration of the blood glucose levels in diabetic mice. The utilization of FGF-2 showed increased contents of insulin in the islet grafts and revealed a similar pattern as that of normal healthy mice in IPGTT. In contrast, the transplantation of islets without FGF-2 supplementation showed poor revascularization and failed to control the blood glucose levels in the diabetic mice.
Rivas-Carrillo
Jorge David
JD
Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Navarro-Alvarez
Nalu
N
Soto-Gutierrez
Alejandro
A
Okitsu
Teru
T
Chen
Yong
Y
Tabata
Yasuhiko
Y
Misawa
Haruo
H
Noguchi
Hirofumi
H
Matsumoto
Shinichi
S
Tanaka
Noriaki
N
Kobayashi
Naoya
N
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000097:blood / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000627:therapeutic use*; D005780:Gelatin / Q000737:chemistry; D005951:Glucose Tolerance Test; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D016222:Fibroblast Growth Factor 2; D005780:Gelatin