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Updated: Mar 3, 2026
Longitudinal In Vivo Imaging and Quantification of Human Pancreatic Islet Grafting and Contributing Host Cells in the Anterior Eye Chamber
Published on: June 11, 2020
Xenotransplantation of layer-by-layer encapsulated non-human primate islets with a specified immunosuppressive drug
Muhammad R Haque1, Jiwoong Kim1, Hyojun Park2
1Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with humans. LbL with three-layers of polyethylene glycol (PEG) molecules (SH-6-arm-PEG-NHS, 6-arm-PEG-catechol and linear PEG-SH) showed a uniform nano-shielding on islets without the loss of viability or function of islets. An immunosuppressive drug protocol was also combined to improve the survival rate of the transplanted islets in vivo. A xenorecipient (C57BL/6 mice) of LbL islet transplanted along with our immunosuppressive drug protocol showed 100% survival rate for 150days after transplantation. On the other hand, naked islet recipients showed poor survival time of 5.5±1.4days without drugs and 77.5±42days with the drug protocol. Immunohistochemistry of the transplanted grafts and serum cytokine concentration demonstrated less immunogenicity in the LbL islet transplanted recipients compared with the naked islet ones.
Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with humans. LbL with three-layers of polyethylene glycol (PEG) molecules (SH-6-arm-PEG-NHS, 6-arm-PEG-catechol and linear PEG-SH) showed a uniform nano-shielding on islets without the loss of viability or function of islets. An immunosuppressive drug protocol was also combined to improve the survival rate of the transplanted islets in vivo. A xenorecipient (C57BL/6 mice) of LbL islet transplanted along with our immunosuppressive drug protocol showed 100% survival rate for 150days after transplantation. On the other hand, naked islet recipients showed poor survival time of 5.5±1.4days without drugs and 77.5±42days with the drug protocol. Immunohistochemistry of the transplanted grafts and serum cytokine concentration demonstrated less immunogenicity in the LbL islet transplanted recipients compared with the naked islet ones.
