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Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects

Oxidative stress and inflammation are major drivers in the pathogenesis and progression of pulmonary fibrosis (PF). The mesenchymal stem cell (MSC) secretome has regenerative potential and immunomodulatory functions. Human embryonic stem cell (hESC)-derived MSC-like immune and matrix regulatory cell...

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Autores principales: Hu, Wenfeng, Yang, Jiali, Xue, Jing, Ma, Jia, Wu, Shuang, Wang, Jing, Xu, Ranran, Wei, Jun, Wang, Yujiong, Wang, Shuyan, Liu, Xiaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953085/
https://www.ncbi.nlm.nih.gov/pubmed/36830999
http://dx.doi.org/10.3390/biomedicines11020463
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author Hu, Wenfeng
Yang, Jiali
Xue, Jing
Ma, Jia
Wu, Shuang
Wang, Jing
Xu, Ranran
Wei, Jun
Wang, Yujiong
Wang, Shuyan
Liu, Xiaoming
author_facet Hu, Wenfeng
Yang, Jiali
Xue, Jing
Ma, Jia
Wu, Shuang
Wang, Jing
Xu, Ranran
Wei, Jun
Wang, Yujiong
Wang, Shuyan
Liu, Xiaoming
author_sort Hu, Wenfeng
collection PubMed
description Oxidative stress and inflammation are major drivers in the pathogenesis and progression of pulmonary fibrosis (PF). The mesenchymal stem cell (MSC) secretome has regenerative potential and immunomodulatory functions. Human embryonic stem cell (hESC)-derived MSC-like immune and matrix regulatory cells (IMRCs) are manufacturable with large-scale good manufacturing practice (GMP) preparation. In the present study, the antioxidative and anti-inflammatory properties and the therapeutic effect of the secretome of hESC-MSC-IMRC-derived conditioned culture medium (CM) (hESC-MSC-IMRC-CM) were investigated. Results revealed the capacities of hESC-MSC-IMRC-CM to reduce bleomycin (BLM)-induced reactive oxygen species (ROS), extracellular matrix (ECM) deposition, and epithelial–mesenchymal transition (EMT) in A549 cells. The administration of concentrated hESC-MSC-IMRC-CM significantly alleviated the pathogenesis of PF in lungs of BLM-injured mice, as accessed by pathohistological changes and the expression of ECM and EMT. A mechanistic study further demonstrated that the hESC-MSC-IMRC-CM was able to inhibit BLM-induced ROS and pro-inflammatory cytokines, accompanied by a reduced expression of Nox4, Nrf2, Ho-1, and components of the Tlr4/MyD88 signaling cascade. These results provide a proof of concept for the hESC-MSC-IMRC-derived secretome treatment of PF, in part mediated by their antioxidative and anti-inflammatory effects. This study thus reinforces the development of ready-to-use, cell-free hESC-MSC-IMRC secretome biomedicine for the treatment of PF in clinical settings.
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spelling pubmed-99530852023-02-25 Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects Hu, Wenfeng Yang, Jiali Xue, Jing Ma, Jia Wu, Shuang Wang, Jing Xu, Ranran Wei, Jun Wang, Yujiong Wang, Shuyan Liu, Xiaoming Biomedicines Article Oxidative stress and inflammation are major drivers in the pathogenesis and progression of pulmonary fibrosis (PF). The mesenchymal stem cell (MSC) secretome has regenerative potential and immunomodulatory functions. Human embryonic stem cell (hESC)-derived MSC-like immune and matrix regulatory cells (IMRCs) are manufacturable with large-scale good manufacturing practice (GMP) preparation. In the present study, the antioxidative and anti-inflammatory properties and the therapeutic effect of the secretome of hESC-MSC-IMRC-derived conditioned culture medium (CM) (hESC-MSC-IMRC-CM) were investigated. Results revealed the capacities of hESC-MSC-IMRC-CM to reduce bleomycin (BLM)-induced reactive oxygen species (ROS), extracellular matrix (ECM) deposition, and epithelial–mesenchymal transition (EMT) in A549 cells. The administration of concentrated hESC-MSC-IMRC-CM significantly alleviated the pathogenesis of PF in lungs of BLM-injured mice, as accessed by pathohistological changes and the expression of ECM and EMT. A mechanistic study further demonstrated that the hESC-MSC-IMRC-CM was able to inhibit BLM-induced ROS and pro-inflammatory cytokines, accompanied by a reduced expression of Nox4, Nrf2, Ho-1, and components of the Tlr4/MyD88 signaling cascade. These results provide a proof of concept for the hESC-MSC-IMRC-derived secretome treatment of PF, in part mediated by their antioxidative and anti-inflammatory effects. This study thus reinforces the development of ready-to-use, cell-free hESC-MSC-IMRC secretome biomedicine for the treatment of PF in clinical settings. MDPI 2023-02-05 /pmc/articles/PMC9953085/ /pubmed/36830999 http://dx.doi.org/10.3390/biomedicines11020463 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hu, Wenfeng
Yang, Jiali
Xue, Jing
Ma, Jia
Wu, Shuang
Wang, Jing
Xu, Ranran
Wei, Jun
Wang, Yujiong
Wang, Shuyan
Liu, Xiaoming
Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects
title Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects
title_full Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects
title_fullStr Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects
title_full_unstemmed Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects
title_short Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects
title_sort secretome of hesc-derived msc-like immune and matrix regulatory cells mitigate pulmonary fibrosis through antioxidant and anti-inflammatory effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953085/
https://www.ncbi.nlm.nih.gov/pubmed/36830999
http://dx.doi.org/10.3390/biomedicines11020463
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