Transplantation of human matrix metalloproteinase-1 gene-modified bone marrow-derived mesenchymal stem cell attenuates CCL4-induced liver fibrosis in rats

Background: The application of mesenchymal stem cell (MSC) therapy in liver fibrosis treatment has been increasingly investigated in recent years. MSCs obtained from a variety of sources (e.g. bone marrow, umbilical cord blood and adipose tissue) have been studied and have achieved remarkable results. In this study, we compared the effects of adipose-derived mesenchymal stem cells (AD-MSC) transplantation with bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in a mouse model of liver fibrosis, induced by carbon tetrachloride (CCl4). Methods: Eight-week old mice were treated with CCl4 for 11 weeks to induce liver fibrosis then 5x105 cells were transplanted into mice via the tail vein. Results: After 21 days of transplantation, the results showed that the stem cell treated groups ameliorated better than the placebo group. MSC treated groups showed reduced AST and ALT levels, down-regulated expression of extracellular matrix (ECM) genes, and improved liver histopathology. Both sources of MSCs (bone marrow and adipose tissue) were effective in the mouse model of liver fibrosis. Conclusion: Our results also indicated that AD-MSC transplantation in mice accelerated liver regeneration better than BM-MSC transplantation.

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Treatment Efficiency of Different Routes of Bone Marrow-Derived Mesenchymal Stem Cell Injection in Rat Liver Fibrosis Model

Cellular Physiology and Biochemistry ◽

10.1159/000492558 ◽

2018 ◽

Vol 48 (5) ◽

pp. 2161-2171 ◽

Cited By ~ 12

Author(s):

Naglaa K. Idriss ◽

Hayam G. Sayyed ◽

Amany Osama ◽

Dina Sabry

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Stem Cell ◽

Growth Factor ◽

Liver Fibrosis ◽

Mesenchymal Stem Cell ◽

Rat Liver ◽

Enzyme Linked Immunosorbent Assay ◽

Rat Liver Fibrosis ◽

Recovery Group

Background/Aims: The most appropriate route for bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in the management of liver fibrosis remains controversial. This study investigated the therapeutic efficacy of intravenous and intrasplenic BM-MSC transplantation on carbon tetrachloride (CCl4)-induced rat liver fibrosis. Methods: Fifty rats were divided into 5 groups (n = 10 rats per group): healthy control group, CCl4 group, CCl4/ recovery group, CCl4/BM-MSC intravenous group, and CCl4/BM-MSC intrasplenic group. BM-MSCs were isolated, labeled with green fluorescent protein (GFP), and injected into fibrotic rats either intravenously or intrasplenically. Gene expression of interleukins (IL-1β and IL-6), interferon (INF)-γ, hepatic growth factor, and the hepatocyte-specific marker cytokeratin 18 was estimated by quantitative real-time reverse transcription-polymerase chain reaction. Vascular endothelial growth factor and connective tissue growth factor was detected by western blot analysis and enzyme-linked immunosorbent assay, respectively. At 2 weeks after intravenous and intrasplenic BM-MSC injections, GFP-positive cells were detected in liver tissue. Results: Both routes achieved a similar enhancement of liver function, which was confirmed by histopathological examination. The intravenous route was more effective than the intrasplenic route in reducing gene expression levels of IL-1β, IL-6, and INF-γ. However, fibrotic changes were still observed in the recovery group. Conclusion: Intravenous BM-MSC injection was an efficient and appropriate route for BM-MSC transplantation for the management of liver fibrosis.

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Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression

Cell Biology International ◽

10.1042/cbi20090386 ◽

2010 ◽

Vol 34 (6) ◽

pp. 601-605 ◽

Cited By ~ 69

Author(s):

Vahideh Rabani ◽

Mansoureh Shahsavani ◽

Marzieh Gharavi ◽

Abbas Piryaei ◽

Zahra Azhdari ◽

...

Keyword(s):

Stem Cell ◽

Carbon Tetrachloride ◽

Liver Fibrosis ◽

Mesenchymal Stem Cell ◽

Matrix Metalloproteinase ◽

Infusion Therapy

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Complex effect of continuous curcumin exposure on human bone marrow‐derived mesenchymal stem cell regenerative properties through matrix metalloproteinase regulation

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/bcpt.13477 ◽

2020 ◽

Vol 128 (1) ◽

pp. 141-153

Author(s):

Qichen Yang ◽

Samantha Antonio Leong ◽

Kwok Ping Chan ◽

Xiang‐Ling Yuan ◽

Tsz Kin Ng

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Matrix Metalloproteinase ◽

Human Bone ◽

Human Bone Marrow ◽

Complex Effect

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The Effect of Mesenchymal Stem Cell Wharton's Jelly on Matrix Metalloproteinase-1 and Interleukin-4 Levels in Osteoarthritis Rat Model

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.152 ◽

2019 ◽

Vol 7 (4) ◽

pp. 529-535 ◽

Cited By ~ 1

Author(s):

Endrinaldi Endrinaldi ◽

Eryati Darwin ◽

Nasrul Zubir ◽

Gusti Revilla

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Matrix Metalloproteinase ◽

Joint Disease ◽

Interleukin 4 ◽

Target Component ◽

Control Group ◽

Control Group Design ◽

Matrix Metalloproteinase 1

BACKGROUND: Osteoarthritis (OA) is generally considered a degenerative joint disease caused by biomechanical changes and the ageing process. In OA pathogenesis, the development of OA is thought to be regulated largely by excess matrix metalloproteinase (MMP), which contributes to the degradation of extracellular matrices such as MMP-1 and Interleukin-4. AIM: This study aims to prove the influence of Mesenchymal Stem Cell Wharton Jelly on decreasing MMP-1 levels and increasing IL-4 which is a specific target as a target component in cases of osteoarthritis in vivo. MATERIAL AND METHODS: This research is an experimental study with the design of Post-Test-Only Control Group Design. The sample consisted of 16 OA rats as a control group and 16 OA rats treated with MSC-WJ as a treatment group. OA induction is done by injection of monosodium iodoacetate (MIA) into the intra-articular right knee. Giving MSC-WJ is done in the third week after MIA induction. The serum MMP-1 and IL-4 levels were measured after 3 weeks treated with MSC-WJ using the ELISA method. The statistical test used is an independent t-test. The value of p < 0.05 was said to be statistically significant. RESULTS: The result showed that serum MMP-1 levels were higher in the group treated with MSC-WJ than in the control group (p < 0.05). Serum IL-4 levels were higher in the group treated with MSC-WJ than in the control group (p < 0.05). CONCLUSION: This study concluded that MSC-WJ increased MMP-1 levels and IL-4 levels in serum OA rats. MSC-WJ showed a negative effect on MMP-1 in the serum of OA rats.

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