TY - JOUR
T1 - 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
AU - Zavaro, Mor
AU - Dangot, Ayelet
AU - Bar-Lev, Tali Hana
AU - Amit, Odelia
AU - Avivi, Irit
AU - Ram, Ron
AU - Aharon, Anat
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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.
AB - 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.
KW - chronic graft-versus-host diseases (cGVHD)
KW - extracellular vesicles (EVs)
KW - fibrosis
KW - inflammation
KW - placenta
UR - http://www.scopus.com/inward/record.url?scp=85159289033&partnerID=8YFLogxK
U2 - 10.3390/ijms24098126
DO - 10.3390/ijms24098126
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C2 - 37175831
AN - SCOPUS:85159289033
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 9
M1 - 8126
ER -