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Session: Technical Session VII

Bioengineering IV

Friday, July 12, 2024
8:00 AM – 10:00 AM CET
Location: Sala Italia
Liver fibrosis is a major global health concern, contributing to 3.5% of worldwide mortality. With limited liver transplant availability, exploring alternative therapies is urgent. MSC-derived EVs (MSC-EVs) present a promising treatment avenue. These nanosized particles reduce inflammation, promote liver cell repair, and offer biocompatibility, low immunogenicity, and opportunities for tailored optimization to improve functionality.
This study aims to engineer MSC-EVs to target hepatic stellate cells (HSCs), key contributors to liver fibrosis. Through a tailored "sponge" system on their surface, this innovative platform effectively suppresses fibrosis in vivo. We explored the interaction between EVs and serum proteins post systemic exposure. After isolating and fluorescently labelling EVs, we assessed their kinetics and uptake in liver subpopulations post intravenous injection. Proteomics and bioinformatics helped identify proteins enhancing HSC uptake. Using one such protein, we developed the innovative "sponge" EV system, evaluated for anti-inflammatory and liver fibrosis suppression. We discovered that albumin adsorption on EV surfaces enhances uptake by HSCs and delays body clearance. Leveraging this, we engineered an EV-albumin sponge system amplifying albumin adsorption upon systemic delivery. This platform improves HSC targeting, mediates anti-inflammation, suppresses HSC activation, and reduces collagen deposition, demonstrated in both in vitro and in vivo studies.
We present a liver cell-targeting and anti-fibrotic delivery complex enabled by a novel albumin sponge technique. This pioneering approach introduces innovative drug loading strategies using surface sponges to enhance therapeutic efficacy.