Role of Glycans in Equine Endometrial Cell Uptake of Extracellular Vesicles Derived from Amniotic Mesenchymal Stromal Cells.
Abstract: Extracellular vesicles (EVs) are important mediators of cell-cell communication thanks to their ability to transfer their bioactive cargo, thus regulating a variety of physiological contexts. EVs derived from amniotic mesenchymal/stromal cells (eAMC-EVs) are internalized by equine endometrial cells (eECs) with positive effects on regenerative medicine treatments. As the cellular uptake of EVs is influenced by the glycan profile of both EVs and target cells, this study is focused on the role of surface glycans in the uptake of eAMC-EVs by recipient eECs. Equine ECs were obtained by enzymatic digestion of uteri from healthy mares. Equine AMC-EVs were isolated from amniotic cell cultures according to a standardized protocol. The glycan pattern was studied using a panel of lectins in combination with fucosidase and neuraminidase treatment. Both eECs and eAMC-EVs expressed N-linked high mannose glycans, as well as fucosylated and sialylated glycans. All these glycans were involved in the uptake of eAMC-EVs by eECs. The internalization of eAMC-EVs was strongly reduced after cleavage of α1,2-linked fucose and α2,3/α2,6-linked sialic acids. These results demonstrate that surface glycans are involved in the internalization of eAMC-EVs by eECs and that fucosylated and sialylated glycans are highly relevant in the transfer of bioactive molecules with effects on regenerative medicine treatments.
Publication Date: 2025-02-19 PubMed ID: 40004247PubMed Central: PMC11855797DOI: 10.3390/ijms26041784Google Scholar: Lookup
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Summary
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This research investigates how surface sugars, or glycans, play a role in the absorption of extracellular vesicles (EVs) from amniotic mesenchymal stromal cells by equine endometrial cells. The study finds that certain types of glycans strongly influence this process and thus may impact treatments in regenerative medicine.
Study Objective and Methodology
- The purpose of the study was to understand how surface sugars or glycans are involved in the absorption of extracellular vesicles (eAMC-EVs) from amniotic mesenchymal/stromal cells by equine endometrial cells (eECs). Glycan profiles can influence cellular uptake of EVs so this study focused on the role of glycans in this interaction.
- The researchers collected equine endometrial cells from healthy horse wombs using an enzymatic digestion process. They isolated eAMC-EVs from horse amniotic cell cultures following a standard protocol.
- They then studied the sugar pattern using a panel of lectins, sugar-binding proteins, combined with fucosidase and neuraminidase treatment. This method enabled them to identify the types of glycans present on both the eECs and the eAMC-EVs.
Results and Findings
- The researchers discovered that N-linked high mannose glycans, fucosylated and sialylated glycans were expressed by both the equine endometrial cells (eECs) and amniotic mesenchymal/stromal cell-derived extracellular vesicles (eAMC-EVs).
- All these glycans were involved in the uptake of eAMC-EVs by eECs, confirming the vital role glycans play in cellular uptake of EVs.
- Further, the internalization process of eAMC-EVs was significantly reduced after the cleavage of α1,2-linked fucose and α2,3/α2,6-linked sialic acids, thereby confirming the importance of fucosylated and sialylated glycans in the process.
Conclusion and Implications
- The study concludes that surface glycans, specifically fucosylated and sialylated glycans, are crucial for the internalization of eAMC-EVs by eECs.
- This finding is highly significant for regenerative medicine treatments, as extracellular vesicles are known to carry bioactive molecules that can regulate physiological processes. Thus, understanding the role of glycans in the uptake of these vesicles can help improve the effectiveness of such treatments.
Cite This Article
APA
Gaspari G, Lange-Consiglio A, Cremonesi F, Desantis S.
(2025).
Role of Glycans in Equine Endometrial Cell Uptake of Extracellular Vesicles Derived from Amniotic Mesenchymal Stromal Cells.
Int J Mol Sci, 26(4), 1784.
https://doi.org/10.3390/ijms26041784 Publication
Researcher Affiliations
- Laboratory of Reproduction and Regenerative Medicine, Department of Veterinary Medicine and Animal Science (DIVAS), University of Milan, 26900 Lodi, Italy.
- Laboratory of Reproduction and Regenerative Medicine, Department of Veterinary Medicine and Animal Science (DIVAS), University of Milan, 26900 Lodi, Italy.
- Laboratory of Reproduction and Regenerative Medicine, Department of Veterinary Medicine and Animal Science (DIVAS), University of Milan, 26900 Lodi, Italy.
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, 70010 Valenzano, Italy.
MeSH Terms
- Animals
- Extracellular Vesicles / metabolism
- Horses
- Female
- Endometrium / metabolism
- Endometrium / cytology
- Mesenchymal Stem Cells / metabolism
- Mesenchymal Stem Cells / cytology
- Polysaccharides / metabolism
- Amnion / metabolism
- Amnion / cytology
- Cells, Cultured
- Fucose / metabolism
Grant Funding
- PRIN202223FCREM_01 / Ministero dell'Istruzione, dell'Universitu00e0 e della Ricerca (MUR), Bando PRIN 2022 Settore LS9
Conflict of Interest Statement
The authors declare no conflicts of interest.
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