间充质干细胞抑制转化生长因子-β促进肝纤维化动物模型肝脏再生

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL Universa Medicina Pub Date : 2021-02-26 DOI:10.18051/UNIVMED.2021.V40.29-35
N. A. C. Sa’dyah, A. Putra, Bayu Tirta Dirja, N. Hidayah, Salma Yasmine Azzahara, Risky Candra Satria Irawan
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引用次数: 2

摘要

肝纤维化(LF)是由肝组织中不受调节的慢性伤口愈合过程引起的。转化生长因子-β (TGF-β)是促进LF的主要细胞因子,通过激活静止的肝星状细胞(hsc)成肌成纤维细胞(MFs)和增加细胞外基质(ECM)沉积,如胶原,导致瘢痕组织发育。间充质干细胞(Mesenchymal stem cells, MSCs)具有免疫调节能力,可以通过抑制TGF-β作为一种新的治疗方法来修复和再生LF。本研究旨在通过抑制TGF-β水平在肝纤维化动物模型中的作用,而不形成疤痕,特别是在增殖期。方法本研究采用完全随机设计,样本量为24例。雄性Sprague Dawley大鼠腹腔注射四氯化碳(CCl4),每周2次,连续8周诱导LF。将大鼠随机分为阴性对照、CCl4组、CCl4 + msc处理组T1和T2,剂量分别为1 × 106和2 × 106细胞。采用酶联免疫吸附法(ELISA)检测TGF-β水平。采用单因素方差分析和最小显著性差异(LSD)对数据进行分析。结果骨髓间充质干细胞给药后第7天TGF水平降低。MSC T1、T2组TGF-β水平均较对照组显著降低(p<0.05)。T2对TGF-β的抑制能力最优,且较T1更显著。结论mscs可抑制肝纤维化大鼠TGF水平。
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Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model
IntroductionLiver 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.MethodsIn 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. ResultsThe 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.ConclusionMSCs can suppress TGF levels in liver fibrosis induced rats.
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Universa Medicina
Universa Medicina MEDICINE, GENERAL & INTERNAL-
自引率
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发文量
27
审稿时长
20 weeks
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