The Role of Extracellular Vesicles (EVs) in Chronic Graft vs. Host Disease, and the Potential Function of Placental Cell-Derived EVs as a Therapeutic Tool

Mor Zavaro, Ayelet Dangot, Tali Hana Bar-Lev, Odelia Amit, Irit Avivi, Ron Ram, Anat Aharon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Chronic graft-versus-host disease (cGVHD) presents with dermal inflammation and fibrosis. We investigated the characteristics of extracellular vesicles (EVs) obtained from cGVHD patients, and their potential effects on human dermal fibroblast (NHDF) cells. The anti-inflammatory and anti-fibrotic effects of placental EVs were also explored given their known anti-inflammatory properties. Fourteen cGVHD patients’ EVs contained higher levels of fibrosis-related proteins, TGFβ and α-smooth muscle actin (αSMA), compared to EVs from thirteen healthy subjects. The exposure of NHDF cells to the patients’ EVs increased the NHDF cells’ TGFβ and αSMA expressions. Placental EVs derived from placental-expanded cells (PLX) (Pluri Inc.) and human villous trophoblast (HVT) cells expressing the mesenchymal markers CD29, CD73, and CD105, penetrated into both the epidermal keratinocytes (HACATs) and NHDF cells. Stimulation of the HACAT cells with cytokine TNFα/INFγ (0.01–0.1 ng/µL) reduced cell proliferation, while the addition of placental EVs attenuated this effect, increasing and normalizing cell proliferation. The treatment of NHDF cells with a combination of TGFβ and placental HVT EVs reduced the stimulatory effects of TGFβ on αSMA production by over 40% (p = 0.0286). In summary, EVs from patients with cGVHD can serve as a biomarker for the cGVHD state. Placental EVs may be used to regulate dermal inflammation and fibrosis, warranting further investigation of their therapeutic potential.

Original languageEnglish
Article number8126
JournalInternational Journal of Molecular Sciences
Volume24
Issue number9
DOIs
StatePublished - 1 May 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Funding

This research was funded by the Israel Ministry of Health, Estates Fund, grant number 20200575, with matching funding from Pluri Inc.

FundersFunder number
Israel Ministry of Health, Estates Fund20200575
Pluri Inc.

    Keywords

    • chronic graft-versus-host diseases (cGVHD)
    • extracellular vesicles (EVs)
    • fibrosis
    • inflammation
    • placenta

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