Divergent Proteomic Profiles and Uptake Mechanisms\nof Exosomes Derived from Human Dental Pulp Stem Cells, Endothelial\nCells, and Fibroblasts

Effective intercellular communication\nis crucial for tissue repair\nand regeneration, with exosomes playing a key role in mediating these\nprocesses by transferring proteins, lipids, and nucleic acids between\ncells. This study explored the mechanisms underlying the uptake of\nexosomes derived from human dental pulp stem cells (hDPSCs), human\numbilical vein endothelial cells (HUVECs), and human fibroblasts (HFBs).\nOur findings revealed that hDPSCs exhibited the greatest capacity\nfor exosome uptake across all three cell types. Moreover, exosomes\noriginating from hDPSCs were also taken up in the highest amounts\nby all three cell types. Proteomic analysis uncovered significant\ndifferences in protein expression among exosomes from these different\ncell types, particularly in proteins related to endocytosis. Clathrin-dependent\nendocytosis emerged as the primary pathway for exosome uptake in hDPSCs\nand HUVECs, while HFBs appeared to use a different mechanism. Additionally,\nproteins such as fibronectin and tetraspanins were found to be highly\nexpressed in hDPSC-derived exosomes, suggesting their potential involvement\nin exosome–cell interactions. This study offers new insights\ninto exosome uptake mechanisms and highlights the potential of exosomes\nin advancing tissue engineering and regenerative medicine.