Abstract
Mesenchymal stem cells (MSCs) play a crucial role in regenerative medicine due to their regenerative potential. However, traditional MSC-based therapies are hindered by issues such as microvascular obstruction and low cell survival after transplantation. Exosomes derived from MSCs (MSC-Exo) provide a cell-free, nanoscale alternative, mitigating these risks and offering therapeutic potential for liver diseases. Nonetheless, the functional variability of MSCs from different sources complicates their clinical application. Stem cells derived from human exfoliated deciduous teeth (SHED) offer advantages such as ease of procurement and robust proliferative capacity, but their secretome, particularly SHED-Exo, remains underexplored in the context of liver disease therapy. This study analyzed MSC-Exo from various sources via small RNA sequencing to identify differences in microRNA profiles, aiding in the selection of optimal MSC sources for clinical use. SHED-Exo was subsequently tested in an acute liver injury model, showing notable regenerative effects, including enhanced hepatocyte proliferation, macrophage polarization, and reduced inflammation. Despite strong liver-targeting properties, the rapid hepatic clearance of SHED-Exo limits its effectiveness in chronic liver diseases. To address this challenge, a GelMA-based hydrogel was developed for in situ delivery, ensuring sustained release and enhanced antifibrotic efficacy, providing a promising strategy for chronic liver disease management.