Effect of glucose toxicity on intraportal tilapia islet xenotransplantation in nude mice.
BACKGROUND
Discordant xenogeneic islets transplanted intraportally into athymic nude rats experience primary non-function and are rapidly destroyed. Recently, it has been reported that adult porcine islets transplanted intraportally into nude mice are also rapidly destroyed and that this constitutes a new model for instant blood-mediated inflammatory reaction (IBMIR).


METHODS
Tilapia (fish) islets were harvested, mechanically broken into mammalian islet-sized fragments, cultured for 48 h, and transplanted via the portal vein into athymic or euthymic mice.


RESULTS
There were several groups of recipient mice. Streptozotocin-diabetic nude mice received 400 islets via the portal vein (n = 12). Recipients were killed when hyperglycemic (>200 mg/dl); livers and native pancreases were examined histologically. Mean graft survival time, based on function, was 5.4 +/- 1.2 days; at autopsy, histology showed occasional viable islets. We also performed a group of transplants in non-diabetic nude mice (n = 6) and then killed the recipients 2 or 4 weeks later; all had abundant viable, well-granulated islet grafts based on histology. Therefore, the intraportal environs in nude mice are not incompatible with discordant fish islets; rather, it appears as if hyperglycemia adversely affects the intraportal islet grafts (i.e. ''glucose toxicity''). To test this hypothesis, transplants were performed into non-diabetic nude mice and allowed to engraft for either 3 days (n = 6) or 10 days (n = 8) prior to injection of streptozotocin (200 to 220 mg/kg i.v.) to destroy the beta-cells in the recipients' native islets (n.b. tilapia islets are exceedingly resistant to streptozotocin); these recipients were followed for 28 days post-transplantation (or until hyperglycemic) and then killed for histology. Mean graft function exceeded 25 days for both groups and viable well-granulated, tilapia islets grafts were readily identified in all recipients; in all but one, the native pancreases were markedly beta-cell depleted -- confirming that normoglycemia was due to functional fish islet xenografts.


CONCLUSIONS
Our results suggest that ''glucose toxicity'' plays a role in the immediate demise of intraportal tilapia islet xenografts.
Al-Jazaeri
Ayman
A
Department of Pathology, IWK Health Centre, Halifax, Nova Scotia, B3H 1V7, Canada.
Xu
Bao-You
BY
Yang
Hua
H
Macneil
Danielle
D
Leventhal
Joseph R
JR
Wright
James R
JR
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000601:surgery*; D005947:Glucose / Q000378:metabolism*; D006084:Graft Rejection / Q000473:pathology; D006085:Graft Survival; D007515:Islets of Langerhans / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008099:Liver / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011169:Portal Vein; D017210:Tilapia; D013997:Time Factors; D014183:Transplantation, Heterologous
D005947:Glucose