Characterization of the transcriptome in isolated and transplanted mouse pancreatic islets

Abstract

The transplantation of pancreatic islets is an option for therapeutic management of hypoglycemia unawareness in select patients with type 1 diabetes mellitus. Characteristics of the transcriptome of freshly isolated islets, islet allografts, and islet isograft are reported in the literature. However, no single experiment has undertaken a comparison of the islet allograft to isograft. Potential implications of the latter are the use in diagnosis of rejection and to discover the molecular pathways in islet allograft dysfunction after transplant. Here, the mouse model of islet transplant is used to characterize the transcriptome of freshly isolated islets and compare islet graft in an isogeneic vs. allogeneic host using an Affymetrix GeneChip® Array assay. A set of islet associated transcripts (IAT) was developed, and subsequently shown to have high level of expression in islet allografts and isografts harvested either five- or ten-days after transplant. Furthermore, specific analysis of transcriptome differences between islet isografts and pre-rejection allografts (ten-day), reveal a series of islet rejection associated transcripts (IRAT). Nearly half of IRAT show overlap with previously described pathogenesis based transcript sets identified in the setting of mouse kidney allograft rejection. The novel transcripts identified to be associated with islet rejection include those involved in chemotaxis or lymphocyte function. Although use of biopsy based monitoring of humans islet transplants remains difficult at the present time, this study provides proof of principle for a transcriptome based technique for islet graft rejection monitoring and describes the transcripts associated with islet graft dysfunction.