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

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