Associate Researcher MKbiotech Co., Ltd. MKbiotech Ltd. Inc., Republic of Korea
Abstract: Cell-derived extracellular vesicles (EVs) are mediators of intercellular communication capable of delivering biologically active molecules. EVs inherit specific properties from their parent cells, which define their composition, biological activity, and therapeutic potential. Stem cell-derived EVs are particularly enriched in molecules related to tissue regeneration, making them highly valuable for therapeutic applications. Placental mesenchymal stem cells (MSCs) can be obtained easily and noninvasively after childbirth, offering unique therapeutic advantages such as low immunogenicity, promotion of tissue repair, reduction of inflammation, and enhancement of angiogenesis. In this study, we investigated the therapeutic potential of a thermogel complex (EVs-thermogel) composed of placental MSC-derived EVs, designed to overcome the limitations of stem cell delivery and retain therapeutic agents at wound sites for extended periods. Placental MSC-derived EVs exhibit superior capabilities in cell proliferation and immuno-modulation, and when blended with a thermossensitivity sol-gel matrix, their therapeutic efficiency is enhanced. The temperature-dependent sol-gel transition was achieved through hexanoylation of glycol chitosan (HGC). The placental MSC were characterized through analysis of cell proliferation, differentiation, and the expression of stem cell markers. The EVs-thermogel, formulated by the physical amalgamation of HGC and EVs, was optimized to evaluate its physical properties. This EVs-thermogel demonstrated no cytotoxic effects and promoted cell proliferation in co-culture environments. Its regenerative capacity was validated through positive outcomes in in vitro scratch assays and angiogenesis evaluations. It was confirmed biocompatibility through blood wettability properites. These results confirmed that EVs-thermogel is effective in tissue regeneration and holds significant promise for commercialization as a therapeutic treatment.
Funding Source: This work was supported by KOITA (Korea Industrial Technology Association) grant funded by MSIT (Korea Ministry of Environment). [R&DCENTER Capability Enhancement Project, grant number: 1711199718]