Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

Introduction Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increase...

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Main Authors: Nur Anna C Sa’dyah, Agung Putra, Bayu Tirta Dirja, Nurul Hidayah, Salma Yasmine Azzahara, Risky Candra Satria Irawan
Format: Article
Language:English
Published: Faculty of Medicine Trisakti University 2021-02-01
Series:Universa Medicina
Subjects:
Online Access:https://univmed.org/ejurnal/index.php/medicina/article/view/1079
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author Nur Anna C Sa’dyah
Agung Putra
Bayu Tirta Dirja
Nurul Hidayah
Salma Yasmine Azzahara
Risky Candra Satria Irawan
author_facet Nur Anna C Sa’dyah
Agung Putra
Bayu Tirta Dirja
Nurul Hidayah
Salma Yasmine Azzahara
Risky Candra Satria Irawan
author_sort Nur Anna C Sa’dyah
collection DOAJ
description Introduction Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase. Methods In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. Results The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p<0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1. Conclusion MSCs can suppress TGF levels in liver fibrosis induced rats.
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spelling doaj.art-e394dc94cd5b489e8cd2d321c4fab2b62022-12-21T22:33:25ZengFaculty of Medicine Trisakti UniversityUniversa Medicina1907-30622407-22302021-02-0140110.18051/UnivMed.2021.v40.29-35429Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal modelNur Anna C Sa’dyah0Agung Putra1Bayu Tirta Dirja2Nurul Hidayah3Salma Yasmine Azzahara4Risky Candra Satria Irawan5Department of Internal Medicine, Medical Faculty, Sultan Agung Islamic University (UNISSULA) Semarang, Central JavaStem Cell and Cancer Research Universitas Islam Sultan AgungDepartment of Microbiology, Medical Faculty, Mataram University, West Nusa TenggaraStem Cell and Cancer Research (SCCR), Medical Faculty, Sultan Agung Islamic University (UNISSULA) Semarang, Central JavaStem Cell and Cancer Research (SCCR), Medical Faculty, Sultan Agung Islamic University (UNISSULA) Semarang, Central JavaStem Cell and Cancer Research (SCCR), Medical Faculty, Sultan Agung Islamic University (UNISSULA) Semarang, Central JavaIntroduction Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase. Methods In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. Results The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p<0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1. Conclusion MSCs can suppress TGF levels in liver fibrosis induced rats.https://univmed.org/ejurnal/index.php/medicina/article/view/1079Liver fibrosismesenchymal stem cellstransforming growth factor-βrats
spellingShingle Nur Anna C Sa’dyah
Agung Putra
Bayu Tirta Dirja
Nurul Hidayah
Salma Yasmine Azzahara
Risky Candra Satria Irawan
Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model
Universa Medicina
Liver fibrosis
mesenchymal stem cells
transforming growth factor-β
rats
title Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model
title_full Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model
title_fullStr Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model
title_full_unstemmed Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model
title_short Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model
title_sort suppression of transforming growth factor β by mesenchymal stem cells accelerates liver regeneration in liver fibrosis animal model
topic Liver fibrosis
mesenchymal stem cells
transforming growth factor-β
rats
url https://univmed.org/ejurnal/index.php/medicina/article/view/1079
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