title: Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression.
abstract: BACKGROUND
  The recurrence of autoimmunity and allograft rejection act as major barriers to the widespread use of islet transplantation as a cure for type 1 diabetes. The aim of this study was to evaluate the feasibility of immunoisolation by use of an agarose microcapsule to prevent autoimmune recurrence after islet transplantation.
  
  
  METHODS
  Highly purified islets were isolated from 6- to 8-week-old prediabetic male nonobese diabetic (NOD) mice and microencapsulated in 5% agarose hydrogel as a semipermeable membrane. Islet function was evaluated by a syngeneic islet transplantation model, in which islets were transplanted into spontaneously diabetic NOD mice.
  
  
  RESULTS
  The nonencapsulated islet grafts were destroyed and diabetes recurred within 2 weeks after transplantation in all 12 mice. In contrast, 13 of the 16 mice that underwent transplantation with microencapsulated islets maintained normoglycemia for more than 100 days after islet transplantation. Histologic examination of the nonencapsulated islet grafts showed massive mononuclear cellular infiltration with beta-cell destruction. In contrast, the microencapsulated islets showed well-granulated beta cells with no mononuclear cellular infiltration around the microcapsules or in the accompanying blood capillaries between the microcapsules.
  
  
  CONCLUSIONS
  Agarose microcapsules were able to completely protect NOD islet isografts from autoimmune destruction in the syngeneic islet transplantation model.
authors.affiliation: First Department of Surgery, Nara Medical University, Kashihara, Nara, Japan. tsunehirokobayashi@hotmail.com.
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Aomatsu
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kin
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kanehiro
authors.forename: Michiyoshi
authors.initials: M
authors.lastname: Hisanaga
authors.forename: Saiho
authors.initials: S
authors.lastname: Ko
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagao
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002214:Capsules; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005951:Glucose Tolerance Test; D006085:Graft Survival; D007165:Immunosuppression Therapy; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009852:Omentum; D012685:Sepharose; D016042:Transplantation, Heterotopic
chemical_list: D002214:Capsules; D012685:Sepharose