Effect of glucose toxicity on intraportal tilapia islet xenotransplantation in nude mice

Ayman Al-Jazaeri, Bao You Xu, Hua Yang, Danielle MacNeil, Joseph R. Leventhal, James R. Wright*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 hyperglyceic(> 200 mg/dl); livers and native pancreases were examined histologically. Mean graft survival time, based on function, was 5.4 ± .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 β-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 β-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.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalXenotransplantation
Volume12
Issue number3
DOIs
StatePublished - May 1 2005

Keywords

  • Glucose toxicity
  • IBMIR
  • Islet xenotransplantation
  • Nude mice
  • Portal vein route
  • Primary non-function
  • Superoxide radicals
  • Teleost fish
  • Tilapia

ASJC Scopus subject areas

  • Immunology
  • Transplantation

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