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Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation

Authors :
Prashanth Vallabhajosyula
Atsushi Hirakata
Matthew Weiss
Adam Griesemer
Akira Shimizu
Hanzhou Hong
Andreas Habertheuer
Vaja Tchipashvili
Kazuhiko Yamada
David H. Sachs
Source :
Cell Transplantation, Vol 26 (2017)
Publication Year :
2017
Publisher :
SAGE Publishing, 2017.

Abstract

In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet–kidney (IK) model previously described by our laboratory was utilized. Three experimental donor animals underwent total pancreatectomy and autologous islet transplantation underneath the renal capsule to prepare an IK at a load of ≤1,000 islet equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the engraftment period (fasting blood glucose >250 mg/dL). Three control donor animals underwent partial pancreatectomy (sufficient to maintain normoglycemia during islet engraftment period) and IK preparation. As in vivo functional readout for islet engraftment, the IKs were transplanted across an immunologic minor or class I mismatch barrier into diabetic, nephrectomized recipients at an islet load of ∼4,500 IE/kg recipient weight. A 12-d course of cyclosporine was administered for tolerance induction. All experimental donors became diabetic and showed signs of end organ injury, while control donors maintained normoglycemia. All recipients of IK from both experimental and control donors achieved glycemic control over long-term follow-up, with reversal of diabetic nephropathy and with similar glucose tolerance tests. In this preclinical, large animal model, neither islet engraftment nor subsequent long-term islet function after transplantation appear to be affected by the diabetic state.

Subjects

Subjects :
Medicine

Details

Language :
English
ISSN :
09636897 and 15553892
Volume :
26
Database :
Directory of Open Access Journals
Journal :
Cell Transplantation
Publication Type :
Academic Journal
Accession number :
edsdoj.b5c6b012d12144f0b1784cdd7639723f
Document Type :
article
Full Text :
https://doi.org/10.1177/0963689717732993