Xenotransplantation of layer-by-layer encapsulated non-human primate islets with a specified immunosuppressive drug protocol

• Published in: Journal of controlled release 2017-07, Vol.258, p.10-21
• Main Authors: Haque, Muhammad R., Kim, Jiwoong, Park, Hyojun, Lee, Han Sin, Lee, Kyo Won, Al-Hilal, Taslim A., Jeong, Jee-Heon, Ahn, Cheol-Hee, Lee, Doo Sung, Kim, Sung Joo, Byun, Youngro
• Format: Article
• Language: English
• Subjects: Animals; Catechols - chemistry; Cell Separation; Cells, Immobilized - cytology; Diabetes Mellitus, Experimental - therapy; Graft Survival - drug effects; Humans; Immunosuppressive Agents - therapeutic use; Islets of Langerhans - cytology; Islets of Langerhans Transplantation - methods; Layer-by-layer; Macaca fascicularis; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Non-human primate pancreatic islets; Polyethylene glycol; Polyethylene Glycols - chemistry; Transplantation, Heterologous; Xenotransplantation
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2017.04.021

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. [Display omitted]