Sustained release of hepatocyte growth factor by cationic self-assembling peptide/heparin hybrid hydrogel improves ?-cell survival and function through modulating inflammatory response.

ABSTRACT: Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect ?-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 ?-cell line was treated with tumor necrosis factor ? in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of ?-cells were evaluated. Cationic KLD1R and KLD2R self-assembled to nanofiber hydrogel, which showed higher binding affinity for Hep and HGF because of electrostatic interaction. Slow release of HGF from cationic SAP/Hep gel is a two-step mechanism involving binding affinity with Hep and molecular diffusion. In vitro and in vivo results showed that HGF-loaded KLD2R/Hep gel promoted ?-cell survival and insulin secretion, and inhibited cell apoptosis, cytokine release, T-cell infiltration, and activation of NF?B/p38 MAPK pathways in ?-cells. This study suggested that SAP/Hep gel is a promising carrier for local delivery of bioactive proteins in islet transplantation.

SUBMITTER: Liu S 

PROVIDER: S-EPMC5042198 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature