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Long-term functions of encapsulated islets grafted in nonhuman primates without immunosuppression.

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 (5000-8000 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%±1.5% and 94.3%±5.71% viable β cells in interscapular site and thigh in autologous recipients and 85.6%±4.01% (interscapular site) and 74.1%±12.05% (thigh) viable β cells in allogenic islet recipients. In vivo glucose challenge test revealed significantly increased glucose-stimulated insulin release (P=0.028) in the left thigh with implant (17.58±3.13 mU/L) compared with the thigh without implant (9.86±1.063 mU/L). Insulin and glucagon gene expression was evident in islets recovered from explanted device. CONCLUSIONS:These results indicate that subcutaneous implantation of macroencapsulated islets is minimally invasive and has potential for transplantation without immunosuppression.

journal_name

Transplantation

journal_title

Transplantation

authors

Sasikala M,Rao GV,Vijayalakshmi V,Pradeep R,Pothani S,Kumar PP,Gaddipati R,Sirisha G,Cheemalakonda R,Tandan M,Subramanyam C,Vasudevan S,Reddy DN

doi

10.1097/TP.0b013e31829e26cf

subject

Has Abstract

pub_date

2013-10-15 00:00:00

pages

624-32

issue

eissn

0041-1337

issn

1534-6080

journal_volume

pub_type

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Long-term functions of encapsulated islets grafted in nonhuman primates without immunosuppression.