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Tolerance induction by surface immobilization of Jagged-1 for immunoprotection of pancreatic islets.

Abstract：

:Although transplantation of pancreatic islets is a promising approach for treatment of type 1 diabetes mellitus, the engraftment efficiency of these islets is limited by host immune responses. Extensive efforts have been made to immunoisolate these islets by introducing barriers on the islet surface. To date, these barriers have not successfully protected islets from attack by the immune system. In addition, the inevitable permeability of an islet capsule cannot prevent filtration by proinflammatory cytokines and islet self-antigens. Thus, we have developed a surface engineering approach for localized immonumodulation of the islet microenvironment. Jagged-1 (JAG-1), as a potent immunomodulatory factor, was immobilized on the islet surface by mediation of a double-layer of heterobifunctional poly (ethylene glycol) (PEG). Immobilization and functionality of JAG-1 on PEGylated islet surfaces were established. When co-cultured with splenocytes, the JAG-1 conjugated islets induced a significant increase in regulatory T cells and regulated the cytokine levels produced by immune cells. The results demonstrated that JAG-1 immobilization could improve immunoprotection of pancreatic islets by localized modulation of the immune milieu from an inflammatory to an anti-inflammatory state. We also evaluated the effects of surface modification of these islets by JAG-1 in a xenotransplantation model. The transplanted JAG-1/PEG/islets group showed a significantly reduced blood glucose levels compared with the control group of diabetic mice during the acute phase of the immune response to the transplanted islets. Our results demonstrated that surface modification has the potential to shift the immune system from an inflammatory to anti-inflammatory milieu and may offer a new prospective for immunoprotection of pancreatic islets.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Izadi Z,Hajizadeh-Saffar E,Hadjati J,Habibi-Anbouhi M,Ghanian MH,Sadeghi-Abandansari H,Ashtiani MK,Samsonchi Z,Raoufi M,Moazenchi M,Izadi M,Nejad ASSH,Namdari H,Tahamtani Y,Ostad SN,Akbari-Javar H,Baharvand H

doi

10.1016/j.biomaterials.2018.08.017

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

191-201

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(18)30571-4

journal_volume

182

pub_type

杂志文章

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