Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Background: Although there is a natural mechanism to ameliorate fibrosis in cirrhosis, it becomes weaker as the disease progresses. We believe that mesenchymal stem cell (MSC)-derived exosomes (extracellular vesicles) exert their fibrosis-improving effects by acting on macrophages, which are important for the improvement of fibrosis, and are aiming for clinical application of MSC-derived exosomes.
Methods: We examined the effect of MSC-derived exosomes on macrophages in vitro, and also examined their therapeutic effect in liver fibrosis. tdTomato was adjusted to express on the surface protein of exosomes from MSC, and the kinetics were observed in vitro and in vivo. In order to collect a large amount of exosomes, we used the Tangential Flow Filtration (TFF) technique, compared to the usual ultracentrifuge technique, and evaluated the improvement of fibrosis in a mouse liver fibrosis model. Results: We have previously shown that IFN-γ-stimulated macrophages are the most effective in inducing anti-inflammatory, motile, and phagocytotic tissue repair macrophages in a cirrhotic model of liver fibrosis, Exosomes collected by TFF tripled the amount of exosomes collected and reduced the collection time by a factor of four compared to the ultracentrifugation method. The therapeutic effect of exosomes collected by TFF in the liver fibrosis model was comparable to that of the ultracentrifugal method in terms of reducing liver damage and improving fibrosis.
Conclusions: We believe that the results of this study suggest that MSC-derived exosomes may be able to induce the intrinsic fibrosis-improving effect in vivo by acting on macrophages. We report the status to date, including a series of studies for future clinical use.
