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Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells
BACKGROUND: Mesenchymal stromal cells (MSCs) from various tissues have shown moderate therapeutic efficacy in reversing liver fibrosis in preclinical models. Here, we compared the relative therapeutic potential of pooled, adult human bone marrow (BM)- and neonatal Wharton’s jelly (WJ)-derived MSCs t...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470281/ https://www.ncbi.nlm.nih.gov/pubmed/28610623 http://dx.doi.org/10.1186/s13287-017-0595-1 |
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author | Rengasamy, Mathiyazhagan Singh, Gurbind Fakharuzi, Noor Atiqah Siddikuzzaman Balasubramanian, Sudha Swamynathan, Priyanka Thej, Charan Sasidharan, Gopinath Gupta, Pawan Kumar Das, Anjan Kumar Rahman, Ahmad Zuhairi Abd Fakiruddin, Kamal Shaik Nian, Lim Moon Zakaria, Zubaidah Majumdar, Anish S. |
author_facet | Rengasamy, Mathiyazhagan Singh, Gurbind Fakharuzi, Noor Atiqah Siddikuzzaman Balasubramanian, Sudha Swamynathan, Priyanka Thej, Charan Sasidharan, Gopinath Gupta, Pawan Kumar Das, Anjan Kumar Rahman, Ahmad Zuhairi Abd Fakiruddin, Kamal Shaik Nian, Lim Moon Zakaria, Zubaidah Majumdar, Anish S. |
author_sort | Rengasamy, Mathiyazhagan |
collection | PubMed |
description | BACKGROUND: Mesenchymal stromal cells (MSCs) from various tissues have shown moderate therapeutic efficacy in reversing liver fibrosis in preclinical models. Here, we compared the relative therapeutic potential of pooled, adult human bone marrow (BM)- and neonatal Wharton’s jelly (WJ)-derived MSCs to treat CCl(4)-induced liver fibrosis in rats. METHODS: Sprague-Dawley rats were injected with CCl(4) for 8 weeks to induce irreversible liver fibrosis. Ex-vivo expanded, pooled human MSCs obtained from BM and WJ were intravenously administered into rats with liver fibrosis at a dose of 10 × 10(6) cells/animal. Sham control and vehicle-treated animals served as negative and disease controls, respectively. The animals were sacrificed at 30 and 70 days after cell transplantation and hepatic-hydroxyproline content, histopathological, and immunohistochemical analyses were performed. RESULTS: BM-MSCs treatment showed a marked reduction in liver fibrosis as determined by Masson’s trichrome and Sirius red staining as compared to those treated with the vehicle. Furthermore, hepatic-hydroxyproline content and percentage collagen proportionate area were found to be significantly lower in the BM-MSCs-treated group. In contrast, WJ-MSCs treatment showed less reduction of fibrosis at both time points. Immunohistochemical analysis of BM-MSCs-treated liver samples showed a reduction in α-SMA(+) myofibroblasts and increased number of EpCAM(+) hepatic progenitor cells, along with Ki-67(+) and human matrix metalloprotease-1(+) (MMP-1(+)) cells as compared to WJ-MSCs-treated rat livers. CONCLUSIONS: Our findings suggest that BM-MSCs are more effective than WJ-MSCs in treating liver fibrosis in a CCl(4)-induced model in rats. The superior therapeutic activity of BM-MSCs may be attributed to their expression of certain MMPs and angiogenic factors. |
format | Online Article Text |
id | pubmed-5470281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54702812017-06-19 Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells Rengasamy, Mathiyazhagan Singh, Gurbind Fakharuzi, Noor Atiqah Siddikuzzaman Balasubramanian, Sudha Swamynathan, Priyanka Thej, Charan Sasidharan, Gopinath Gupta, Pawan Kumar Das, Anjan Kumar Rahman, Ahmad Zuhairi Abd Fakiruddin, Kamal Shaik Nian, Lim Moon Zakaria, Zubaidah Majumdar, Anish S. Stem Cell Res Ther Research BACKGROUND: Mesenchymal stromal cells (MSCs) from various tissues have shown moderate therapeutic efficacy in reversing liver fibrosis in preclinical models. Here, we compared the relative therapeutic potential of pooled, adult human bone marrow (BM)- and neonatal Wharton’s jelly (WJ)-derived MSCs to treat CCl(4)-induced liver fibrosis in rats. METHODS: Sprague-Dawley rats were injected with CCl(4) for 8 weeks to induce irreversible liver fibrosis. Ex-vivo expanded, pooled human MSCs obtained from BM and WJ were intravenously administered into rats with liver fibrosis at a dose of 10 × 10(6) cells/animal. Sham control and vehicle-treated animals served as negative and disease controls, respectively. The animals were sacrificed at 30 and 70 days after cell transplantation and hepatic-hydroxyproline content, histopathological, and immunohistochemical analyses were performed. RESULTS: BM-MSCs treatment showed a marked reduction in liver fibrosis as determined by Masson’s trichrome and Sirius red staining as compared to those treated with the vehicle. Furthermore, hepatic-hydroxyproline content and percentage collagen proportionate area were found to be significantly lower in the BM-MSCs-treated group. In contrast, WJ-MSCs treatment showed less reduction of fibrosis at both time points. Immunohistochemical analysis of BM-MSCs-treated liver samples showed a reduction in α-SMA(+) myofibroblasts and increased number of EpCAM(+) hepatic progenitor cells, along with Ki-67(+) and human matrix metalloprotease-1(+) (MMP-1(+)) cells as compared to WJ-MSCs-treated rat livers. CONCLUSIONS: Our findings suggest that BM-MSCs are more effective than WJ-MSCs in treating liver fibrosis in a CCl(4)-induced model in rats. The superior therapeutic activity of BM-MSCs may be attributed to their expression of certain MMPs and angiogenic factors. BioMed Central 2017-06-13 /pmc/articles/PMC5470281/ /pubmed/28610623 http://dx.doi.org/10.1186/s13287-017-0595-1 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. |
spellingShingle | Research Rengasamy, Mathiyazhagan Singh, Gurbind Fakharuzi, Noor Atiqah Siddikuzzaman Balasubramanian, Sudha Swamynathan, Priyanka Thej, Charan Sasidharan, Gopinath Gupta, Pawan Kumar Das, Anjan Kumar Rahman, Ahmad Zuhairi Abd Fakiruddin, Kamal Shaik Nian, Lim Moon Zakaria, Zubaidah Majumdar, Anish S. Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells |
title | Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells |
title_full | Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells |
title_fullStr | Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells |
title_full_unstemmed | Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells |
title_short | Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells |
title_sort | transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than wharton’s jelly mesenchymal stromal cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470281/ https://www.ncbi.nlm.nih.gov/pubmed/28610623 http://dx.doi.org/10.1186/s13287-017-0595-1 |
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