Long-term survival of nonhuman primate islets implanted in an omental pouch on a biodegradable scaffold.
The aim of this study was to test whether an omental pouch can be used as an alternative site for islet implantation in diabetic monkeys. Here we report the successful engraftment of islets in diabetic cynomolgus monkeys when loaded on a synthetic biodegradable scaffold and placed in an omental pouch. One autologous and five allogeneic diabetic monkey transplants under the cover of steroid-free immune suppression (SFIS) were undertaken. Fasting blood glucose (FBG) and C-peptide (CP), exogenous insulin requirements (EIR), intravenous glucose tolerance test (IVGTT), A1C and histopathology were used to assess islet engraftment and survival. All animals achieved CP levels > 1.0 ng/mL following transplant, a 66-92% posttransplant decrease in EIR and reduced A1C. Following graft removal, CP became negative and histopathological analysis of the explanted grafts demonstrated well-granulated and well-vascularized, insulin-positive islets, surrounded by T-cell subsets and macrophages. Compared to intrahepatic allogeneic islet transplants (n = 20), there was a delayed engraftment for omental pouch recipients but similar levels of CP production were ultimately achieved, with a broad range of IEQ/kg transplanted in both sites. Our results suggest this extrahepatic transplantation site has potential as an alternative site for clinical islet cell transplantation.
Berman
D M
DM
Diabetes Research Institute, Miami, FL, USA. dberman2@med.miami.edu
O'Neil
J J
JJ
Coffey
L C K
LC
Chaffanjon
P C J
PC
Kenyon
N M
NM
Ruiz
P
P
Pileggi
A
A
Ricordi
C
C
Kenyon
Norma S
NS
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006085:Graft Survival; D016381:Islets of Langerhans Transplantation; D008252:Macaca fascicularis; D009852:Omentum; D013311:Streptozocin
D013311:Streptozocin