Optimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys

Abstract Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship...

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Autores principales:	Geun Soo Kim, Chan Woo Cho, Jong Hyun Lee, Du Yeon Shin, Han Sin Lee, Kyo Won Lee, Yeongbeen Kwon, Jae Sung Kim, Heung-Mo Yang, Sung Joo Kim, Jae Berm Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/386c95a3a3c44343810ce598f940de59
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spelling	oai:doaj.org-article:386c95a3a3c44343810ce598f940de592021-12-02T16:45:39ZOptimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys10.1038/s41598-021-88166-y2045-2322https://doaj.org/article/386c95a3a3c44343810ce598f940de592021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88166-yhttps://doaj.org/toc/2045-2322Abstract Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3+ T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.Geun Soo KimChan Woo ChoJong Hyun LeeDu Yeon ShinHan Sin LeeKyo Won LeeYeongbeen KwonJae Sung KimHeung-Mo YangSung Joo KimJae Berm ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Geun Soo Kim Chan Woo Cho Jong Hyun Lee Du Yeon Shin Han Sin Lee Kyo Won Lee Yeongbeen Kwon Jae Sung Kim Heung-Mo Yang Sung Joo Kim Jae Berm Park Optimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys
description	Abstract Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3+ T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.
format	article
author	Geun Soo Kim Chan Woo Cho Jong Hyun Lee Du Yeon Shin Han Sin Lee Kyo Won Lee Yeongbeen Kwon Jae Sung Kim Heung-Mo Yang Sung Joo Kim Jae Berm Park
author_facet	Geun Soo Kim Chan Woo Cho Jong Hyun Lee Du Yeon Shin Han Sin Lee Kyo Won Lee Yeongbeen Kwon Jae Sung Kim Heung-Mo Yang Sung Joo Kim Jae Berm Park
author_sort	Geun Soo Kim
title	Optimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys
title_short	Optimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys
title_full	Optimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys
title_fullStr	Optimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys
title_full_unstemmed	Optimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys
title_sort	optimal allogeneic islet dose for transplantation in insulin-dependent diabetic macaca fascicularis monkeys
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/386c95a3a3c44343810ce598f940de59
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Optimal allogeneic islet dose for transplantation in insulin-dependent diabetic Macaca fascicularis monkeys

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