Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression.
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.
Kobayashi
Tsunehiro
T
First Department of Surgery, Nara Medical University, Kashihara, Nara, Japan. tsunehirokobayashi@hotmail.com.
Aomatsu
Yukio
Y
Iwata
Hiroo
H
Kin
Tatsuya
T
Kanehiro
Hiromichi
H
Hisanaga
Michiyoshi
M
Ko
Saiho
S
Nagao
Mitsuo
M
Nakajima
Yoshiyuki
Y
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
D002214:Capsules; D012685:Sepharose