title: Sustained release of hepatocyte growth factor by cationic self-assembling peptide/heparin hybrid hydrogel improves β-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 β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-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 β-cell survival and insulin secretion, and inhibited cell apoptosis, cytokine release, T-cell infiltration, and activation of NFκB/p38 MAPK pathways in β-cells. This study suggested that SAP/Hep gel is a promising carrier for local delivery of bioactive proteins in islet transplantation.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, West China Hospital.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute for Nanobiomedical Technology and Membrane Biology, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, West China Hospital.
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, West China Hospital.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, West China Hospital.
authors.forename: Jingping
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology*; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002942:Circular Dichroism; D016207:Cytokines / Q000378:metabolism; D003692:Delayed-Action Preparations; D004058:Diffusion; D005947:Glucose / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy*; D007328:Insulin / Q000737:chemistry; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects; D016381:Islets of Langerhans Transplantation; D008027:Light; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D057139:Nanofibers / Q000737:chemistry; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity
chemical_list: D002412:Cations; D016207:Cytokines; D003692:Delayed-Action Preparations; C066855:HGF protein, human; D020100:Hydrogels; D007328:Insulin; D017228:Hepatocyte Growth Factor; D006493:Heparin; D005947:Glucose
keywords: HGF; inflammation; islet transplantation; self-assembling peptide; slow release