Effectiveness of Mesenchymal Stem Cells and Bovine Colostrum on Decreasing Tumor Necrosis Factor-Α Levels and Enhancement of Macrophages M2 in Remnant Liver

Ezra Endria Gunadi; Yan  Wisnu Prajoko; Agung Putra

doi:10.3889/oamjms.2021.7902

Authors

Ezra Endria Gunadi Department of Biomedical, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
Yan Wisnu Prajoko Department of Biomedical, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
Agung Putra Stem Cells and Cancer Research, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia https://orcid.org/0000-0003-4261-9437

DOI:

https://doi.org/10.3889/oamjms.2021.7902

Keywords:

Mesenchymal stem cells, Bovine colostrum, Tumor necrosis factor-Α, Macrophages M2, Liver

Abstract

BACKGROUND: Mesenchymal stem cells (MSCs) and bovine colostrum are potential therapies for the treatment of various degenerative and immune diseases.

AIM: This study aimed to analyze the effect of MSCs on levels of tumor necrosis factor-Α (TNF-α) and macrophages M2 in the liver fibrosis of Wistar rats after 50% resection.

METHODS: This study is a quasi-experimental post-test-only control group design to analyze the effect of giving bovine colostrum and MSCs to test animals on the process of regeneration of the remaining 50% liver with fibrosis. The study was conducted at the Stem Cell and Cancer Research Universitas Sultan Agung. The number of samples used was 40 male Wistar rats. The independent variables included MSC 1.000.0000 cells and bovine colostrum at a dose of 15 μL/g. Dependent variables used were macrophages M2 and levels of TNF-α ELISA.

RESULTS: TNF-α levels on day 3 were (p = 0.001), day 7 were (p = 0.01), and day 10 were (p = 0.01) in liver tissue in various study groups analyzed using ELISA on day three*. The results showed differences which were significant between the control and treatment groups (p < 0.05). The expression of CD163 marked brown in liver tissue had more expression than the control group.

CONCLUSION: The combination of MSCs and bovine colostrum can reduce TNF-α levels and significantly increase macrophages expression in the liver fibrosis of Wistar rats after 50% resection on the 3_th, 7_th, and 10_thdays.

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References

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

Sabry HS, El-Hendy AA, Mohammed HI, Essa AS, Abdel-Aziz AS. Study of serum tumor necrosis factor-α _in patients with liver cirrhosis. Menoufia Med J. 2015;28(2):525. DOI: https://doi.org/10.4103/1110-2098.163913

Osawa Y, Kojika E, Hayashi Y, Kimura M, Nishikawa K, Yoshio S, et al. Tumor necrosis factor-α-mediated hepatocyte apoptosis stimulates fibrosis in the steatotic liver in mice. Hepatol Commun. 2018;2(4):407-20. https://doi.org/10.1002/hep4.1158 Mid:29619419 DOI: https://doi.org/10.1002/hep4.1158

Ren G, Chen X, Dong F, Li W, Ren X, Zhang Y, et al. Concise review: Mesenchymal stem cells and translational medicine: Emerging issues. Stem Cells Transl Med. 2012;1(1):51-8. https://doi.org/10.5966/sctm.2011-0019 PMid:23197640 DOI: https://doi.org/10.5966/sctm.2011-0019

Zhao Q, Ren H, Han Z. Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases. J Cell Immunother. 2016;2(1):3-20. DOI: https://doi.org/10.1016/j.jocit.2014.12.001

Berardis S, Sattwika PD, Najimi M, Sokal EM. Use of mesenchymal stem cells to treat liver fibrosis: Current situation and future prospects. World J Gastroenterol. 2015;21(3):742-58. https://doi.org/10.3748/wjg.v21.i3.742 PMid:25624709 DOI: https://doi.org/10.3748/wjg.v21.i3.742

Eom YW, Shim KY, Baik SK. Mesenchymal stem cell therapy for liver fibrosis. The Korean J Intern Med. 2015;30(5):580-9. https://doi.org/10.3904/kjim.2015.30.5.580 PMid:26354051 DOI: https://doi.org/10.3904/kjim.2015.30.5.580

Luo XY, Meng XJ, Cao DC, Wang W, Zhou K, Li L, et al. Transplantation of bone marrow mesenchymal stromal cells attenuates liver fibrosis in mice by regulating macrophage subtypes. Stem Cell Res Ther. 2019;10(1):16. https://doi.org/10.1186/s13287-018-1122-8 PMid:30635047 DOI: https://doi.org/10.1186/s13287-018-1122-8

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

Playford RJ, Weiser MJ. Bovine colostrum: Its constituents and uses. Nutrients. 2021;13(1):265. https://doi.org/10.3390/nu13010265 PMid:33477653 DOI: https://doi.org/10.3390/nu13010265

Sinn DH, Gwak GY, Kwon YJ, Paik SW. Anti-fibrotic effect of bovine colostrum in carbon tetrachloride-induced hepatic fibrosis. Precis Future Med. 2017;1(2):88-94. DOI: https://doi.org/10.23838/pfm.2017.00121

Peverill W, Powell LW, Skoien R. Evolving concepts in the pathogenesis of NASH: Beyond steatosis and inflammation. Int J Mol Sci. 2014;15(5):8591-638. https://doi.org/10.3390/ijms15058591 PMid:24830559 DOI: https://doi.org/10.3390/ijms15058591

Shimamoto K, Hayashi H, Taniai E, Morita R, Imaoka M, Ishii Y, et al. Antioxidant N-acetyl-L-cysteine (NAC) supplementation reduces reactive oxygen species (ROS)-mediated hepatocellular tumor promotion of indole-3-carbinol (I3C) in rats. J Toxicol Sci. 2011;36(6):775-86. https://doi.org/10.2131/jts.36.775 PMid:22129741 DOI: https://doi.org/10.2131/jts.36.775

Sun M, Kisseleva T. Reversibility of liver fibrosis. Clin Res Hepatol Gastroenterol. 2015;39 Suppl 1:S60-3. https://doi.org/10.1016/j.clinre.2015.06.015 PMid:26206574 DOI: https://doi.org/10.1016/j.clinre.2015.06.015

Pellicoro A, Ramachandran P, Iredale JP. Reversibility of liver fibrosis. Fibrogenesis Tissue Repair. 2012;5 Suppl 1:S26. https://doi.org/10.1186/1755-1536-5-S1-S26 PMid:23259590 DOI: https://doi.org/10.1186/1755-1536-5-S1-S26

Yang YM, Seki E. TNFα _in liver fibrosis. Curr Pathobiol Rep. 2015;3(4):253-61. https://doi.org/10.1007/s40139-015-0093-z PMid:26726307 DOI: https://doi.org/10.1007/s40139-015-0093-z

Zhang L, Wang Y, Wu G, Xiong W, Gu W, Wang CY. Macrophages: Friend or foe in idiopathic pulmonary fibrosis? Respir Res. 2018;19(1):170. DOI: https://doi.org/10.1186/s12931-018-0864-2

Navegantes KC, de Souza Gomes R, Pereira PA, Czaikoski PG, Azevedo CH, Monteiro MC. Immune modulation of some autoimmune diseases: The critical role of macrophages and neutrophils in the innate and adaptive immunity. J Transl Med. 2017;15(1):36. https://doi.org/10.1186/s12967-017-1141-8 PMid:28202039 DOI: https://doi.org/10.1186/s12967-017-1141-8

Berardis S, Lombard C, Evraerts J, El Taghdouini A, Rosseels V, Sancho-Bru P, et al. Gene expression profiling and secretome analysis differentiate adult-derived human liver stem/progenitor cells and human hepatic stellate cells. PLoS One. 2014;9(1):e86137. https://doi.org/10.1371/journal.pone.0086137 PMid:24516514 DOI: https://doi.org/10.1371/journal.pone.0086137

Lee CA, Sinha S, Fitzpatrick E, Dhawan A. Hepatocyte transplantation and advancements in alternative cell sources for liver-based regenerative medicine. J Mol Med. 2018;96(6):469-81. https://doi.org/10.1007/s00109-018-1638-5 PMid:29691598 DOI: https://doi.org/10.1007/s00109-018-1638-5

Rengasamy M, Singh G, Fakharuzi NA, Balasubramanian S, Swamynathan P, Thej C, et al. Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells. Stem Cell Res Ther. 2017;8(1):143. https://doi.org/10.1186/s13287-017-0595-1 PMid:28610623 DOI: https://doi.org/10.1186/s13287-017-0595-1

Braga TT, Agudelo JS, Camara NO. Macrophages during the fibrotic process: M2 as friend and foe. Front Immunol. 2015;6:602. https://doi.org/10.3389/fimmu.2015.00602 PMid:26635814 DOI: https://doi.org/10.3389/fimmu.2015.00602

Chaudhuri B, Pramanik K. Key aspects of the mesenchymal stem cells (MSCs) in tissue engineering for in vitro skeletal muscle regeneration. Biotechnol Mol Biol Rev. 2012;7(1):5-15. DOI: https://doi.org/10.5897/BMBR11.020

Yang H, Sun L, Pang Y, Hu D, Xu H, Mao S, et al. Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure. Gut. 2021;70(3):567-74. https://doi.org/10.1136/gutjnl-2019-319960 PMid:32434830 DOI: https://doi.org/10.1136/gutjnl-2019-319960

Michalopoulos GK, Khan Z. Liver regeneration, growth factors, and amphiregulin. Gastroenterology. 2005;128(2):503-6. https://doi.org/10.1053/j.gastro.2004.12.039 PMid:15685562 DOI: https://doi.org/10.1053/j.gastro.2004.12.039

Nelsen CJ, Rickheim DG, Timchenko NA, Stanley MW, Albrecht JH. Transient expression of cyclin D1 is sufficient to promote hepatocyte replication and liver growth in vivo. Cancer Res. 2001;61(23):8564-8. PMid:11731443

Kuramitsu K, Sverdlov DY, Liu SB, Csizmadia E, Burkly L, Schuppan D, et al. Failure of fibrotic liver regeneration in mice is linked to a severe fibrogenic response driven by hepatic progenitor cell activation. Am J Pathol. 2013;183(1):182-94. https://doi.org/10.1016/j.ajpath.2013.03.018 PMid:23680654 DOI: https://doi.org/10.1016/j.ajpath.2013.03.018

Katoonizadeh A, Nevens F, Verslype C, Pirenne J, Roskams T. Liver regeneration in acute severe liver impairment: A clinicopathological correlation study. Liver Int. 2006;26(10):1225-33. https://doi.org/10.1111/j.1478-3231.2006.01377.x PMid:17105588 DOI: https://doi.org/10.1111/j.1478-3231.2006.01377.x