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Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice
Published on: July 23, 2017
Effects of surface camouflaged islet transplantation on pathophysiological progression in a db/db type 2 diabetic
Jee-Heon Jeong1, Simmyung Yook, Haeshin Lee
1Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Abstract:
To investigate the inhibition effects of pancreatic islet transplantation on the progression of obese type 2 diabetes, we analyzed the effects of surface camouflaged islet transplantation on delaying the disease progression in a db/db diabetic mouse model. Surface camouflaged islets using 6-arm-PEG-catechol were transplanted in db/db diabetic mice. The fat accumulation and toxicity in the liver, the expansion of islets in the pancreas, and the size change of abdominal adipocyte were analyzed. In addition, the blood glucose control, insulin levels and immunohistochemical staining of recovered tissues were analyzed after transplantation. Then co-administration of anti-CD154 monoclonal antibody and Tacrolimus (IT group) deterred the pathophysiological progression of obese type 2 diabetes. At day 3 of transplantation, the serum insulin concentration of IT group was increased compared to the db/db diabetic mice group. The immunohistochemical studies demonstrated that the mass of 6-arm-PEG-catechol grafted islet was preserved in the transplantation site for 14 days. Surface modification using 6-arm-PEG-catechol effectively inhibited the immune cell infiltration and activation of host immune cells when immunosuppressive drug was given to the db/db type 2 diabetes mice. Therefore, 6-arm-PEG-catechol grafted islets effectively restored the insulin secretion in islet recipients and prevented the disease progression in type 2 diabetes.
Insights
Surface camouflaged islets effectively restored insulin secretion and prevented disease progression in obese type 2 diabetes. This novel approach using 6-arm-PEG-catechol shows promise for diabetes treatment.
Area of Science:
- Endocrinology
- Immunology
- Biomaterials Science
Background:
- Obese type 2 diabetes is a growing global health concern.
- Pancreatic islet transplantation is a potential treatment but faces challenges with immune rejection and graft survival.
- Developing strategies to improve islet graft survival and function is crucial.
Purpose of the Study:
- To investigate the efficacy of surface camouflaged islet transplantation in inhibiting the progression of obese type 2 diabetes.
- To evaluate the impact of 6-arm-PEG-catechol surface modification on islet graft survival and function in a diabetic mouse model.
Main Methods:
- Surface camouflaged islets using 6-arm-PEG-catechol were transplanted into db/db diabetic mice.
- Evaluated liver fat accumulation, pancreatic islet expansion, and adipocyte size.
- Analyzed blood glucose control, insulin levels, and performed immunohistochemical staining.
Main Results:
- Surface modification with 6-arm-PEG-catechol preserved islet mass for 14 days post-transplantation.
- Transplantation in combination with immunosuppressants (anti-CD154 and Tacrolimus) deterred disease progression.
- Increased serum insulin concentration and restored insulin secretion in recipients.
Conclusions:
- Surface camouflaged islets using 6-arm-PEG-catechol effectively inhibit immune cell infiltration and activation.
- This method enhances islet graft survival and restores insulin secretion, preventing type 2 diabetes progression.
