Mitnala , S. and Rao , V.G. and Venkateshan, V. and Rebala , P. and Pothani , S. and Kumar , P. and Gaddipati , R. and Sirisha , G. and Cheemalakonda , R. and Tandan , M. and Subramanyam , C. and Seshadri, V. and Reddy, N.D. (2013) Long-Term Functions of Encapsulated Islets Grafted in Nonhuman Primates Without Immunosuppression. Transplantation & Volume 96, Number 7, October 15, 2013, 96 (7).

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Abstract

Background. Long-term survival and functions of encapsulated islet grafts need to be evaluated in the absence of immunosuppression. The present study aimed to assess the viability and functions of macroencapsulated islets grafted in nonhuman primates without immunosuppression for 1 year. Methods. Islet transplantations were performed in partially pancreatectomized rhesus monkeys (two autologous and four allogenic) without immunosuppression using immunoisolatory devices. Macroencapsulated islets were implanted subcutaneously (5000Y8000 IEQ/device) at two sites (left thigh and interscapular region) and were explanted at 2, 6, and 12 months after implantation. Staining for viability and apoptosis, in vivo and in vitro glucose-stimulated insulin release, expression of insulin and glucagon genes, and histopathologic examination of the device were used to assess engraftment potential, viability, and functions of islets. Animals were regularly monitored for dietary intake, body weight, and fasting blood glucose levels after islet transplantation. Results. Devices explanted showed vascularization at the end of 2, 6, and 12 months with occasional lymphocytes and minimal fibrosis outside the device. Flow cytometric analysis revealed 97.9%T1.5% and 94.3%T5.71% viable A cells in interscapular site and thigh in autologous recipients and 85.6%T4.01% (interscapular site) and 74.1%T12.05% (thigh) viable A cells in allogenic islet recipients. In vivo glucose challenge test revealed significantly increased glucosestimulated insulin release (P=0.028) in the left thigh with implant (17.58T3.13 mU/L) compared with the thigh without implant (9.86T1.063 mU/L). Insulin and glucagon gene expression was evident in islets recovered from explanted device.

Item Type:	Article
Subjects:	Diabetes
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	13 Apr 2015 10:11
Last Modified:	07 Jul 2015 05:06
URI:	http://nccs.sciencecentral.in/id/eprint/71

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