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Peer-reviewedCC BY 4.0Cells

Recipient Cell Type-Dependent Association of Extracellular Vesicles from Different Cellular Origins

  1. 1Department of Laboratory Medicine, Division of Biomolecular and Cellular Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden
  2. 2Biology Research Center, Research Center, University of Zakho, Zakho 42002, Kurdistan Region, Iraq
  3. 3Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, SE-171 76 Stockholm, Sweden

Abstract

Extracellular vesicles (EVs) are promising nanocarriers for therapeutic delivery; however, the factors influencing their interactions with recipient cells remain incompletely understood. This study investigated recipient-cell-specific EV association using mNG-CD81-labelled EVs derived from HEK293T, SKBR-3, and Yummer cells. EV-associated fluorescence was assessed by flow cytometry following incubation with human epithelial, immune, and murine melanoma cell lines at different doses and time points. Marked differences were observed across recipient-cell types. Liver-derived Huh7 and HepG2 cells exhibited the highest percentages of fluorescence-positive cells among human epithelial cells, whereas parental HEK293T cells showed the lowest. THP-1 cells exhibited greater EV-associated fluorescence than Jurkat cells, while Yummer melanoma cells showed higher fluorescence than B16F10 cells following exposure to HEK293T-derived EVs. Similar recipient-cell patterns were observed with SKBR-3- and Yummer-derived EVs. Notably, Yummer cells exhibited relatively high association with their own EVs, demonstrating that low parental-cell association is not universal. EV-associated fluorescence generally increased with dose and incubation time. Although these findings highlight recipient-cell specificity, the relative contributions of EV donor origin and recipient-cell characteristics remain unresolved. Moreover, flow cytometry cannot distinguish surface-associated from internalized EVs. Together, these findings identify recipient-cell specificity as an important determinant of EV-associated fluorescence, providing a foundation for understanding EV–cell interactions and informing the development of targeted EV-based delivery strategies.

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BibTeX
@article{mamand2026recipient,
  title = {{Recipient Cell Type-Dependent Association of Extracellular Vesicles from Different Cellular Origins}},
  author = {Doste R. Mamand},
  journal = {Cells},
  year = {2026},
  month = nov,
  doi = {10.3390/cells15212010},
  url = {https://www.mdpi.com/2073-4409/15/21/2010},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Recipient Cell Type-Dependent Association of Extracellular Vesicles from Different Cellular Origins
AU  - Doste R. Mamand
PY  - 2026
DA  - 2026/11/04
JO  - Cells
DO  - 10.3390/cells15212010
UR  - https://www.mdpi.com/2073-4409/15/21/2010
AB  - Extracellular vesicles (EVs) are promising nanocarriers for therapeutic delivery; however, the factors influencing their interactions with recipient cells remain incompletely understood. This study investigated recipient-cell-specific EV association using mNG-CD81-labelled EVs derived from HEK293T, SKBR-3, and Yummer cells. EV-associated fluorescence was assessed by flow cytometry following incubation with human epithelial, immune, and murine melanoma cell lines at different doses and time points. Marked differences were observed across recipient-cell types. Liver-derived Huh7 and HepG2 cells exhibited the highest percentages of fluorescence-positive cells among human epithelial cells, whereas parental HEK293T cells showed the lowest. THP-1 cells exhibited greater EV-associated fluorescence than Jurkat cells, while Yummer melanoma cells showed higher fluorescence than B16F10 cells following exposure to HEK293T-derived EVs. Similar recipient-cell patterns were observed with SKBR-3- and Yummer-derived EVs. Notably, Yummer cells exhibited relatively high association with their own EVs, demonstrating that low parental-cell association is not universal. EV-associated fluorescence generally increased with dose and incubation time. Although these findings highlight recipient-cell specificity, the relative contributions of EV donor origin and recipient-cell characteristics remain unresolved. Moreover, flow cytometry cannot distinguish surface-associated from internalized EVs. Together, these findings identify recipient-cell specificity as an important determinant of EV-associated fluorescence, providing a foundation for understanding EV–cell interactions and informing the development of targeted EV-based delivery strategies.
SN  - 2073-4409
ER  -