Journal Article

Exosome inspired photo-triggered gelation hydrogel composite on modulating immune pathogenesis for treating rheumatoid arthritis

Liu, Shiyi, Yang, Yumin, Tang, Xiaoxuan, Rui, Ke, Jiang, Chao, Ling, Jue, Zhu, Qiugang, Shen, Ziwei, Che, Nan, Tian, Jie

2023

Overview

Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and desirable protective effects for attenuating joint destruction still remain challenges. Here, silk fibroin hydrogel encapsulated with olfactory ecto-mesenchymal stem cell-derived exosomes (Exos@SFMA) was photo-crosslinked in situ to yield long-lasting therapeutic effect on modulating the immune microenvironment in RA. This in situ hydrogel system exhibited flexible mechanical properties and excellent biocompatibility for protecting tissue surfaces in joint. Moreover, the promising PD-L1 expression was identified on the exosomes, which potently suppressed Tfh cell polarization via inhibiting the PI3K/AKT pathway. Importantly, Exos@SFMA effectively relieved synovial inflammation and joint destruction by significantly reducing T follicular helper (Tfh) cell response and further suppressing the differentiation of germinal center (GC) B cells into plasma cells. Taken together, this exosome enhanced silk fibroin hydrogel provides an effective strategy for the treatment of RA and other autoimmune diseases.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 1-Phosphatidylinositol 3-kinase / AKT protein / Antiarthritic agents / Arthritis / Arthritis, Rheumatoid - metabolism / Autoimmune diseases / Autoimmune pathogenesis / B cells / Biocompatibility / Biotechnology / Care and treatment / Cartilage / Cell differentiation / Cell organelles / Chemical properties / Chemistry / Chemistry and Materials Science / Colloids in medicine / Destruction / Exosomes / Fibroins - metabolism / Flow cytometry / Health aspects / Humans / Hydrogels / Immunotherapy / In-situ hydrogel / Lymphocytes / Lymphocytes B / Mechanical properties / Mesenchymal stem cells / Microenvironments / Molecular Medicine / Molecular targeted therapy / Nanotechnology / Pathogenesis / PD-L1 protein / Phosphatidylinositol 3-Kinases - metabolism / Plasma cells / Proteins / Rheumatoid arthritis / Rheumatoid factor / Scanning electron microscopy / Silk / Silk fibroin / Stem cells / T follicular helper cells / T-Lymphocytes, Helper-Inducer - metabolism / T-Lymphocytes, Helper-Inducer - pathology / Therapeutics, Experimental