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

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 o...

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Autores principales: Vallabhajosyula, Prashanth, Hirakata, Atsushi, Weiss, Matthew, Griesemer, Adam, Shimizu, Akira, Hong, Hanzhou, Habertheuer, Andreas, Tchipashvili, Vaja, Yamada, Kazuhiko, Sachs, David H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784526/
https://www.ncbi.nlm.nih.gov/pubmed/29338381
http://dx.doi.org/10.1177/0963689717732993
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author Vallabhajosyula, Prashanth
Hirakata, Atsushi
Weiss, Matthew
Griesemer, Adam
Shimizu, Akira
Hong, Hanzhou
Habertheuer, Andreas
Tchipashvili, Vaja
Yamada, Kazuhiko
Sachs, David H.
author_facet Vallabhajosyula, Prashanth
Hirakata, Atsushi
Weiss, Matthew
Griesemer, Adam
Shimizu, Akira
Hong, Hanzhou
Habertheuer, Andreas
Tchipashvili, Vaja
Yamada, Kazuhiko
Sachs, David H.
author_sort Vallabhajosyula, Prashanth
collection PubMed
description 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.
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spelling pubmed-57845262018-01-30 Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation Vallabhajosyula, Prashanth Hirakata, Atsushi Weiss, Matthew Griesemer, Adam Shimizu, Akira Hong, Hanzhou Habertheuer, Andreas Tchipashvili, Vaja Yamada, Kazuhiko Sachs, David H. Cell Transplant Original Articles 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. SAGE Publications 2018-01-16 2017-11 /pmc/articles/PMC5784526/ /pubmed/29338381 http://dx.doi.org/10.1177/0963689717732993 Text en © The Author(s) 2017 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Articles
Vallabhajosyula, Prashanth
Hirakata, Atsushi
Weiss, Matthew
Griesemer, Adam
Shimizu, Akira
Hong, Hanzhou
Habertheuer, Andreas
Tchipashvili, Vaja
Yamada, Kazuhiko
Sachs, David H.
Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation
title Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation
title_full Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation
title_fullStr Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation
title_full_unstemmed Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation
title_short Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation
title_sort effect of the diabetic state on islet engraftment and function in a large animal model of islet–kidney transplantation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784526/
https://www.ncbi.nlm.nih.gov/pubmed/29338381
http://dx.doi.org/10.1177/0963689717732993
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