期刊
JOURNAL OF CONTROLLED RELEASE
卷 258, 期 -, 页码 10-21出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.04.021
关键词
Layer-by-layer; Polyethylene glycol; Non-human primate pancreatic islets; Xenotransplantation
资金
- Korea Health Technology R & D Project of the Korea Health Industry Development Institute (KHIDI) under the Ministry of Health & Welfare, Republic of Korea [HI12C1853]
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 150 days after transplantation. On the other hand, naked islet recipients showed poor survival time of 5.5 +/- 1.4 days without drugs and 77.5 +/- 42 days 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.
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