title: 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.
authors.affiliation: 1 Asian Health Care Foundation, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, Pune, India. 2 National Institute of Nutrition, Hyderabad, India. 3 National Center for Laboratory Animal Sciences, Hyderabad, India. 4 National Center for Cell Sciences, Pune, India. 5 Address correspondence to: Mitnala Sasikala, Ph.D., Asian Health Care Foundation, Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, India.
authors.forename: Mitnala
authors.initials: M
authors.lastname: Sasikala
authors.forename: Guduru Venkat
authors.initials: GV
authors.lastname: Rao
authors.forename: Venkateshan
authors.initials: V
authors.lastname: Vijayalakshmi
authors.forename: Rebala
authors.initials: R
authors.lastname: Pradeep
authors.forename: Suresh
authors.initials: S
authors.lastname: Pothani
authors.forename: Pondugala Pavan
authors.initials: PP
authors.lastname: Kumar
authors.forename: Radhika
authors.initials: R
authors.lastname: Gaddipati
authors.forename: Ganneru
authors.initials: G
authors.lastname: Sirisha
authors.forename: Ramji
authors.initials: R
authors.lastname: Cheemalakonda
authors.forename: Manu
authors.initials: M
authors.lastname: Tandan
authors.forename: Chivukula
authors.initials: C
authors.lastname: Subramanyam
authors.forename: Seshadri
authors.initials: S
authors.lastname: Vasudevan
authors.forename: D Nageshwar
authors.initials: DN
authors.lastname: Reddy
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008253:Macaca mulatta; D008297:Male; D010180:Pancreatectomy; D013997:Time Factors; D054457:Tissue Scaffolds; D014022:Tissue Survival; D023001:Transplantation Tolerance
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D007328:Insulin; D005934:Glucagon