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Volume 12
Issue 8
10.3390/biomedicines12081849
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Article

Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Reversing Hepatic Fibrosis in 3D Liver Spheroids

by
Giulia Chiabotto
,
Armina Semnani
,
Elena Ceccotti
,
Marco Guenza
,
Giovanni Camussi
and
Stefania Bruno
*
Department of Medical Sciences, University of Torino, 10126 Torino, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2024, 12(8), 1849; https://doi.org/10.3390/biomedicines12081849
Submission received: 2 July 2024 / Revised: 8 August 2024 / Accepted: 12 August 2024 / Published: 14 August 2024
(This article belongs to the Special Issue 3D Cell Culture Systems for Biomedical Research)
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Abstract

Hepatic fibrosis, arising from prolonged liver injury, entails the activation of hepatic stellate cells (HSCs) into myofibroblast-like cells expressing alpha-smooth muscle actin (α-SMA), thereby driving extracellular matrix deposition and fibrosis progression. Strategies targeting activated HSC reversal and hepatocyte regeneration show promise for fibrosis management. Previous studies suggest that extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) can suppress HSC activation, but ensuring EV purity is essential for clinical use. This study investigated the effects of MSC-derived EVs cultured in chemically defined conditions on liver spheroids and activated HSCs. Umbilical cord- and bone marrow-derived MSCs were expanded in chemically defined media, and EVs were isolated using filtration and differential ultracentrifugation. The impact of MSC-EVs was evaluated on liver spheroids generated in Sphericalplate 5D™ and on human HSCs, both activated by transforming growth factor beta 1 (TGF-β1). MSC-EVs effectively reduced the expression of profibrotic markers in liver spheroids and activated HSCs induced by TGF-β1 stimulation. These results highlight the potential of MSC-EVs collected under chemically defined conditions to mitigate the activated phenotype of HSCs and liver spheroids, suggesting MSC-EVs as a promising treatment for hepatic fibrosis.
Keywords: mesenchymal stromal cells; extracellular vesicles; liver fibrosis; liver spheroids; hepatic stellate cells; collagen I; chemically defined media mesenchymal stromal cells; extracellular vesicles; liver fibrosis; liver spheroids; hepatic stellate cells; collagen I; chemically defined media
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MDPI and ACS Style

Chiabotto, G.; Semnani, A.; Ceccotti, E.; Guenza, M.; Camussi, G.; Bruno, S. Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Reversing Hepatic Fibrosis in 3D Liver Spheroids. Biomedicines 2024, 12, 1849. https://doi.org/10.3390/biomedicines12081849

AMA Style

Chiabotto G, Semnani A, Ceccotti E, Guenza M, Camussi G, Bruno S. Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Reversing Hepatic Fibrosis in 3D Liver Spheroids. Biomedicines. 2024; 12(8):1849. https://doi.org/10.3390/biomedicines12081849

Chicago/Turabian Style

Chiabotto, Giulia, Armina Semnani, Elena Ceccotti, Marco Guenza, Giovanni Camussi, and Stefania Bruno. 2024. "Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Reversing Hepatic Fibrosis in 3D Liver Spheroids" Biomedicines 12, no. 8: 1849. https://doi.org/10.3390/biomedicines12081849

APA Style

Chiabotto, G., Semnani, A., Ceccotti, E., Guenza, M., Camussi, G., & Bruno, S. (2024). Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Reversing Hepatic Fibrosis in 3D Liver Spheroids. Biomedicines, 12(8), 1849. https://doi.org/10.3390/biomedicines12081849

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