Dong-Na Su
Mesenchymal stem cell-based Smad7 gene therapy for experimental liver cirrhosis
Su, Dong-Na; Wu, Shi-Pin; Xu, Shang-Zhong
Abstract
Background
Bone mesenchymal stem cells (MSCs) can promote liver regeneration and inhibit inflammation and hepatic fibrosis. MSCs also can serve as a vehicle for gene therapy. Smad7 is an essential negative regulatory gene in the TGF-β1/Smad signalling pathway. Activation of TGF-β1/Smad signalling accelerates liver inflammation and fibrosis; we therefore hypothesized that MSCs overexpressing the Smad7 gene might be a new cell therapy approach for treating liver fibrosis via the inhibition of TGF-β1/Smad signalling.
Methods
MSCs were isolated from 6-week-old Wistar rats and transduced with the Smad7 gene using a lentivirus vector. Liver cirrhosis was induced by subcutaneous injection of carbon tetrachloride (CCl4) for 8 weeks. The rats with established liver cirrhosis were treated with Smad7-MSCs by direct injection of cells into the main lobes of the liver. The expression of Smad7, Smad2/3 and fibrosis biomarkers or extracellular matrix proteins and histopathological change were assessed by quantitative PCR, ELISA and Western blotting and staining.
Results
The mRNA and protein level of Smad7 in the recipient liver and serum were increased after treating with Smad-MSCs for 7 and 21 days (P
Citation
Su, D.-N., Wu, S.-P., & Xu, S.-Z. (2020). Mesenchymal stem cell-based Smad7 gene therapy for experimental liver cirrhosis. Stem Cell Research and Therapy, 11(1), Article 395. https://doi.org/10.1186/s13287-020-01911-4
Journal Article Type | Article |
---|---|
Acceptance Date | Aug 27, 2020 |
Online Publication Date | Sep 14, 2020 |
Publication Date | 2020-12 |
Deposit Date | Mar 17, 2021 |
Publicly Available Date | Mar 18, 2021 |
Journal | Stem Cell Research & Therapy |
Print ISSN | 1757-6512 |
Electronic ISSN | 1757-6512 |
Publisher | BioMed Central |
Peer Reviewed | Peer Reviewed |
Volume | 11 |
Issue | 1 |
Article Number | 395 |
DOI | https://doi.org/10.1186/s13287-020-01911-4 |
Keywords | Mesenchymal stem cells; Smad7; Liver cirrhosis; Fibrosis; TGF-β; Gene therapy |
Public URL | https://hull-repository.worktribe.com/output/3741821 |
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Copyright Statement
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the
data made available in this article, unless otherwise stated in a credit line to the data.
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