Microcapsule against hypoxia showed longer graft survival than microcapsule against fibrosis in diabetic mice receiving GalT-KO porcine islet transplantation
Eun Young Lee1, Heon Seok Park2, Ji-Won Kim2, Jong Min Kim3, Poongyeon Lee4, Kun-Ho Yoon1.
1Department of Internal Medicine, Seoul St. Mary’s hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Division of Endocrionology, The Catholic University of Korea, Catholic Research Institute of Medical Science, Seould, Korea; 3Xenotransplantation Research Center, Seoul National University, Seoul, Korea; 4Animal Biotechnology Division, National Institute of Animal Science, Jeonji-si, Korea
Introduction: Fibrosis is one of the most important barrier to improve encapsulated islet graft survival. Hypoxia is another major obstacle for encapsulated islet transplantation. Previously, we have developed several alginate-based microcapsules improving fibrosis (alginate-chitosan) or hypoxia (alginate-perfluorodecalin) and proved their superior effects compared with alginate microcapsule. In this study, we compared long-term graft survival of encapsulated islet with microcapsule against fibrosis or hypoxia in diabetic mice model, using 1,3-galactosyltransferase gene-knockout (GalT-KO) pigs.
Materials and Methods: Islets were isolated form GalT-KO pigs and then encapsulated with alginate-chitosan or alginate-perfluorodecalin microcapsule. To magnify graft survival gap between different microcapsules, marginal doses of islets were transplanted into streoptozotocin-induced diabetic mice intraperitoneally. Blood glucose level were measured for a year. Intraperitoneal glucose tolerance test (IPGTT) was performed at 6 and 12 months after transplantation.
Results: In the alginate-chitosan group, the blood glucose level of diabetic mice decreased after encapsulated islet transplantation. However, blood glucose level increased again within two months in 3 out of 4 mice. In the alginate-perfluorodecalin group, the blood glucose level of diabetic mice decreased after transplantation and maintained normoglycemia more than 6 months. Although blood glucose level tended to increase 6 months after transplantation, it remained below 300 mg/dL by one year. The area under curve (AUC) of IPGTT was similar between two groups at baseline. At 6 months after transplantation, AUC of IPGTT in alginate-perflourodecalin group lower than AUC of alginate-chitosan group. At one year after transplantation, microcapsules were retrieved. Dithizone stain was positive in most retrieved islet and fibrosis was minimal in both groups.
Conclusion: In conclusion, microcapsule against hypoxia showed a longer xenograft survival than microcapsule against fibrosis in diabetic mice.
This work was carried out with the support of "Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ0134532019)" Rural Development Administration, Republic of Korea.
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