The Combination of Mesenchymal Stem Cells and Bovine Colostrum in Reducing α-SMA Expression and NLR Levels in Wistar Rats After 50% Fibrotic Liver Resection

Authors

  • Michael Mawi Hartanto Department of Biomedical Sciences, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
  • Yan Wisnu Prajoko Department of Biomedical Sciences, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
  • Agung Putra Stem Cell and Cancer Research, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia; Department of Pathology, Medical Faculty, Sultan Agung Islamic University, Semarang, Indonesia; Department of Biomedical Science, Medical Faculty, Sultan Agung Islamic University, Semarang, Indonesia https://orcid.org/0000-0003-4261-9437
  • Nur Dina Amalina Stem Cell and Cancer Research, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia; Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Universitas Negeri, Semarang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.10557

Keywords:

Liver fibrosis, α-SMA, Neutrophil lymphocyte ratio, Mesenchymal stem cells, Bovine colostrum

Abstract

Background: Liver fibrogenesis will produce α-smooth muscle actin (α-SMA) expression and a continuous inflammatory process, seen through the neutrophil lymphocyte ratio (NLR). The combination of mesenchymal stem cells and bovine colostrum is a novel strategy for repairing hepatic fibrosis tissue. To assess the combination of mesenchymal stem cells and bovine colostrum to reduce α-SMA expression and NLR levels in Wistar rats after 50% fibrotic liver resection.

Methods: Thirty-six Wistar male rats were randomly divided into 6 groups (sham, control, colostrum, MSCs, and colostrum and MSCs combination). Rats were injected with CCl4 for 8 weeks to induce liver fibrosis then underwent liver resection. NLR levels was determined using Hematology Analyzer, α-SMA expression of myofibroblast was analyzed by immunofluorescence staining.

Results: A significant reduction in NLR levels on day 3 in the treatment group I (1.10), treatment II (0.83), treatment III (0.93) compared to the control group. A significant reduction in NLR levels on day 10 in the treatment group I (0.76), treatment II (0.64), treatment III (0.54) compared to the control group. A significant decrease in α-SMA in treatment group I (0.134), treatment II (0.68), treatment III (0.42) compared to the control group.

Conclusion: In this study, it was found that α-SMA expression, NLR levels on the 3rd and 10th day of administration were reduced in group receiving combination of mesenchymal stem cells and bovine colostrum in the liver of post-resection Wistar rats by 50%.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Kitano M, Bloomston PM. Hepatic stellate cells and microRNAs in pathogenesis of liver fibrosis. J Clin Med. 2016;5(3):38. https://doi.org/10.3390/jcm5030038 PMid:26999230 DOI: https://doi.org/10.3390/jcm5030038

Böttcher K, Pinzani M. Pathophysiology of liver fibrosis and the methodological barriers to the development of anti-fibrogenic agents. Adv Drug Deliv Rev. 2017;121:3-8. https://doi.org/10.1016/j.addr.2017.05.016 PMid:28600202 DOI: https://doi.org/10.1016/j.addr.2017.05.016

Chen L, Zhang C, Chen L, Wang X, Xiang B, Wu X, et al. Human Menstrual blood-derived stem cells ameliorate liver fibrosis in mice by targeting hepatic stellate cells via paracrine mediators. Stem Cells Transl Med. 2017;6(1):272-84. https://doi.org/10.5966/sctm.2015-0265 PMid:28170193 DOI: https://doi.org/10.5966/sctm.2015-0265

Hinz B. The myofibroblast: Paradigm for a mechanically active cell. J Biomech. 2010;43(1):146-55. https://doi.org/10.1016/j.jbiomech.2009.09.020 PMid:19800625 DOI: https://doi.org/10.1016/j.jbiomech.2009.09.020

Rockey DC, Du Q, Shi Z. Smooth muscle α-actin deficiency leads to decreased liver fibrosis via impaired cytoskeletal signaling in hepatic stellate cells. Am J Pathol. 2019;189(11):2209-20. https://doi.org/10.1016/j.ajpath.2019.07.019 PMid:31476284 DOI: https://doi.org/10.1016/j.ajpath.2019.07.019

Kekilli M, Tanoglu A, Sakin YS, Kurt M, Ocal S, Bagci S. Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B? World J Gastroenterol. 2015;21(18):5575-81. https://doi.org/10.3748/wjg.v21.i18.5575 PMid:25987782 DOI: https://doi.org/10.3748/wjg.v21.i18.5575

Ramadan OI, Nasr M, El-Hay OM, Hasan A, Abd-Allah EE, Mahmoud ME, et al. Potential protective effect of Zingiber officinale in comparison to rosuvastatin on high-fat diet-induced non-alcoholic fatty liver disease in rats. Open Access Maced J Med Sci. 2022;10(A):916-23. DOI: https://doi.org/10.3889/oamjms.2022.9643

Jia F, Hu X, Kimura T, Tanaka N. Impact of dietary fat on the progression of liver fibrosis: Lessons from animal and cell studies. Int J Mol Sci. 2021;22(1):10303. https://doi.org/10.3390/ijms221910303 PMid:34638640 DOI: https://doi.org/10.3390/ijms221910303

Kim D, Cho GS, Han C, Park DH, Park HK, Woo DH, et al. Current understanding of stem cell and secretome therapies in liver diseases. Tissue Eng Regen Med. 2017;14(6):653-65. https://doi.org/10.1007/s13770-017-0093-7 PMid:30603518 DOI: https://doi.org/10.1007/s13770-017-0093-7

Restimulia L, Ilyas S, Munir D, Putra A, Madiadipoera T, Farhat F, et al. Rats’ umbilical-cord mesenchymal stem cells ameliorate mast cells and Hsp70 on ovalbumin-induced allergic rhinitis rats. Med Glas (Zenica). 2022;19(1):52-9. https://doi.org/10.17392/1421-21 PMid:35048629

Drawina P, Putra A, Nasihun T, Prajoko YW, Dirja BT, Amalina ND. Increased serial levels of platelet-derived growth factor using hypoxic mesenchymal stem cell-conditioned medium to promote closure acceler-ation in a full-thickness wound. Indones J Biotechnol. 2022;27(1):36. DOI: https://doi.org/10.22146/ijbiotech.64021

Hamra NF, Putra A, Tjipta A, Amalina ND, Nasihun T. Hypoxia mesenchymal stem cells accelerate wound closure improvement by controlling α-smooth muscle actin expression in the full-thickness animal model. Open Access Maced J Med Sci. 2021;9:35-41. DOI: https://doi.org/10.3889/oamjms.2021.5537

Darlan DM, Munir D, Putra A, Alif I, Amalina ND, Jusuf NK, et al. Revealing the decrease of indoleamine 2,3-dioxygenase as a major constituent for B cells survival post-mesenchymal stem cells co-cultured with peripheral blood mononuclear cell (PBMC) of systemic lupus erythematosus (SLE) patients. Med Glas. 2022;19(1):12-8. https://doi.org/10.17392/1414-21 PMid:35048623

Restimulia L, Ilyas S, Munir D, Putra A, Madiadipoera T, Farhat F, et al. The CD4+ CD25+ FoxP3+ Regulatory T Cells Regulated by MSCs Suppress Plasma Cells in a Mouse Model of Allergic Rhinitis. Medical Archives. 202;75(4):256. DOI: https://doi.org/10.5455/medarh.2021.75.256-261

Talele NP, Fradette J, Davies JE, Kapus A, Hinz B. Expression of α-smooth muscle actin determines the fate of mesenchymal stromal cells. Stem Cell Reports. 2015;4(6):1016-30. https://doi.org/10.1016/j.stemcr.2015.05.004 PMid:26028530 DOI: https://doi.org/10.1016/j.stemcr.2015.05.004

Darby IA, Laverdet B, Bonté F, Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301-11. https://doi.org/10.2147/CCID.S50046 PMid:25395868 DOI: https://doi.org/10.2147/CCID.S50046

Ruta VM, Man AM, Alexescu TG, Motoc NS, Tarmure S, Ungur RA, et al. Neutrophil-to-lymphocyte ratio and systemic immune-inflammation index-biomarkers in interstitial lung disease. Medicina (Lithuania). 2020;56(8):381. https://doi.org/10.3390/medicina56080381 PMid:32751302 DOI: https://doi.org/10.3390/medicina56080381

Yilmaz H, Yalcin KS, Namuslu M, Celik HT, Sozen M, Inan O, et al. Neutrophil-lymphocyte ratio (NLR) could be better predictor than C-reactive protein (CRP) for liver fibrosis in non-alcoholic steatohepatitis(NASH). 2015;45(3):278-86. PMid:26116591

Lesmana CR, Kencana Y, Rinaldi I, Kurniawan J, Hasan I, Sulaiman AS, et al. Diagnostic value of neutrophil to lymphocyte ratio in non-alcoholic fatty liver disease evaluated using transient elastography (TE) with controlled attenuated parameter (CAP). Diabetes Metab Syndr Obes. 2022;15:15-22. https://doi.org/10.2147/DMSO.S330526 PMid:35023936 DOI: https://doi.org/10.2147/DMSO.S330526

Darlan DM, Munir D, Jusuf NK, Putra A, Ikhsan R, Alif I. In vitro regulation of IL-6 and TGF-ß by mesenchymal stem cells in systemic lupus erythematosus patients. Med Glas (Zenica). 2020;17(2):408-13.

Prajoko YW, Putra A, Dirja BT, Muhar AM, Amalina ND. The ameliorating effects of MSCs in controlling treg-mediated B-Cell depletion by Indoleamine 2, 3-dioxygenase Induction in PBMC of SLE patients. Open Access Maced J Med Sci. 2022;10(A):6-11.

Sungkar T, Putra A, Lindarto D, Sembiring RJ. Intravenous umbilical cord-derived mesenchymal stem cells transplantation regulates hyaluronic acid and interleukin-10 secretion producing low-grade liver fibrosis in experimental rat. Med Arch. 2020;74(3):177-82. https://doi.org/10.5455/medarh.2020.74.177-182 PMid:32801431 DOI: https://doi.org/10.5455/medarh.2020.74.177-182

Prajoko YW, Putra A, Dirja BT, Muhar AM, Amalina ND. The ameliorating effects of mscs in controlling treg-mediated b-cell depletion by indoleamine 2, 3-dioxygenase induction in PBMC of SLE patients. Open Access Maced J Med Sci. 2022;10:6-11. DOI: https://doi.org/10.3889/oamjms.2022.7487

Gregory AD, Kliment CR, Metz HE, Kim KH, Kargl J, Agostini BA, et al. Neutrophil elastase promotes myofibroblast differentiation in lung fibrosis. J Leukoc Biol. 2015;98(2):143-52. https://doi.org/10.1189/jlb.3HI1014-493R DOI: https://doi.org/10.1189/jlb.3HI1014-493R

Lim JY, Kim BS, Bin RD, Kim TW, Park G, Min CK. The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ _and poly(I: C) priming through promoting the expression of indoleamine 2,3-dioxygenase. Stem Cell Res Ther. 2021;12(1):1-13. DOI: https://doi.org/10.1186/s13287-020-02087-7

El Agha E, Kramann R, Schneider RK, Li X, Seeger W, Humphreys BD, et al. Mesenchymal stem cells in fibrotic disease. Cell Stem Cell. 2017;21(2):166-77. https://doi.org/10.1016/j.stem.2017.07.011 DOI: https://doi.org/10.1016/j.stem.2017.07.011

Putra A, Antari AD, Kustiyah AR, Intan YS, Sadyah NA, Wirawan N, et al. Mesenchymal stem cells accelerate liver regeneration in acute liver failure animal model. Biomed Res Ther. 2018;5(11):2802-10. DOI: https://doi.org/10.15419/bmrat.v5i11.498

Hermansyah D, Putra A, Munir D, Lelo A, Amalina ND, Alif I. Synergistic effect of Curcuma longa extract in combination with Phyllanthus niruri extract in regulating Annexin A2, epidermal growth factor receptor, matrix metalloproteinases, and pyruvate kinase M1/2 signaling pathway on breast cancer stem cell. Open Access Maced J Med Sci. 2021;9(A):271-85. DOI: https://doi.org/10.3889/oamjms.2021.5941

Downloads

Published

2022-12-15

How to Cite

1.
Hartanto MM, Prajoko YW, Putra A, Amalina ND. The Combination of Mesenchymal Stem Cells and Bovine Colostrum in Reducing α-SMA Expression and NLR Levels in Wistar Rats After 50% Fibrotic Liver Resection. Open Access Maced J Med Sci [Internet]. 2022 Dec. 15 [cited 2024 Mar. 29];10(A):1634-9. Available from: https://oamjms.eu/index.php/mjms/article/view/10557

Issue

Section

Pathophysiology

Categories

Most read articles by the same author(s)

1 2 3 > >>