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Abstract
The chronic inflammatory process is a pathological condition characterized by an ongoing active inflammatory response and tissue destruction. Many studies show that chronic inflammation can play a severe role in various age-related diseases, including diabetes, cardiovascular, and autoimmune diseases. One of the important but poorly studied factors affecting the regulation of chronic inflammation is the regulatory activity of MSCs. In this regard, the study of mesenchymal stem cells preventing chronic inflammation in the experiment is an important area of modern pathology.
On the one hand, increased cytokines, such as α-TNF, IL 6, and CRP, are reliable tools in diagnostic different inflammatory processes, especially chronic inflammation. On the other hand, nowadays, we need a more straightforward and not so expensive criterion for this purpose, for instance, a common total blood count and LMR. For the first time, we investigated how trustworthy can be LMR and how possible to use it in chronic inflammation in rats to achieve prognostic goals.
This study investigated the correlation between α-TNF, IL-6, and CRP with LMR in rats' plasma in groups with chronic carrageenan inflammation and chronic inflammation with local injection of MSCs into the affected area. The study involved 132 adult male rats (180-220g), which were divided into groups. The inflammation model was chronic aseptic myositis caused by an intramuscular injection of 10mg λ-carrageenan (Sigma-Aldrich GmbH). Our experimental groups of rats were treated with MSCs (the injection into the inflamed site) in the amount of 1-2 million cells once. Blood sampling was performed from 6 hours to 28 days. We calculated our results using Statistica (data analysis software) version 13. For comparison, we used one-way ANOVA, Turkey's post hoc test, where p <0.05 was considered statistically significant.
In our experiment, the correlation between levels of α-TNF, IL-6, and CRP with lymphocyte-monocyte ratio in rats was described for the first time, demonstrating the suppression of chronic inflammation through MSCs.
References
Soehnlein, O., Steffens, S., Hidalgo, A., Weber, C. (2017). Circadian Control of Inflammatory Processes in Atherosclerosis and Its Complications Arteriosclerosis. Thrombosis, and Vascular Biology, 37, 1022–1028.
Walston, J. D. (2017). The fire of chronic inflammation in older adults: etiologies, consequences, and treatments. Innovation in Aging, 1(1), 961. https://doi.org/10.1093/geroni/igx004.3462
Fougere, B., Boulanger, E., Nourhashemi, F., Guyonnet, S., Cesari, M. (2016). Chronic Inflammation: Accelerator of Biological Aging. The Journals of Gerontology: Series A, 72(9), 1218–1225. https://doi.org/10.1093/gerona/glw240.
Caplan, A. I., Bruder, S. P. (2001). Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. TRENDS in Molecular Medicine, 7(6), 259-64. doi: 10.1016/s1471-4914(01)02016-0.
Szyska , M., Na , I. K. (2016). Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol, 7, 118. doi: 10.3389/fimmu.2016.00118.
Le Blanc, K., Frassoni, F, . Ball, L., Locatelli, F , . Roelofs, H., et al. (2008). Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet, 10, 371(9624), 1579–1586. doi: 10.1016/S0140-6736(08)60690-X.
Griffin, M. D., Elliman, S. J., Cahill, E., English, K., Ceredig, R, Ritter, T. (2013). Concise review: adult mesenchymal stromal cell therapy for inflammatory diseases: how well are we joining the dots? Stem Cells, (10), 2033–2041. doi: 10.1002/stem.1452.
Li-Tzu Wang, Chiao-Hsuan Ting, Men-Luh Yen, Ko-Jiunn Liu, Huey-Kang Sytwu, Kenneth K. Wuand B. Linju Yen. (2016). Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials. Journal of Biomedical Science, 23, art. No. 76. https://doi.org/10.1186/s12929-016-0289-5
Joerg, D., Hoeck, B. Bi., Kurtova, A. V., Noelyn M. Kljavin, Felipe de Sousa e Melo, Bruno Alicke, Hartmut Koeppen, Zora Modrusan, Robert Piskol, Frederic J. de Sauvage. (2017). Stem cell plasticity enables hair regeneration following Lgr5+ cell loss. Nature Cell Biology , 19, 666–676.
Andrea J.De Micheli, Emily J.Laurilliard, Charles L.Heinke, Hiranmayi Ravichandran, Paula Fraczek, SharonSoueid-Baumgarten, Iwijn De Vlaminck, Olivier Elemento, Benjamin D.Cosgrove. (2020). SingleCell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration. Cell reports, 30(10), 3583–3595.
Takehito Ouchi, Taneaki Nakagawa. (2020). Mesenchymal stem cell-based tissue regeneration therapies for periodontitis. Regenerative Therapy , 14, 72–78.
Feng Zhou, Amanda B. Reed-Maldonado, Yan Tan, Huixing Yuan, Dongyi Peng, Lia Banie, Guifang Wang, Jianquan Hou, Guiting Lin, and Tom F. Lue. (2019). Development of Male External Urethral Sphincter and TissueResident Stem/Progenitor Cells in Rats. Stem Cells and Development Mary Ann Liebert, Inc. DOI: 10.1089/scd.2019.0241.
Stephen M.Richardson, Gauthaman Kalamegam, Peter N.Pushpara, Csaba Matta, Adnan Memic, Ali Khademhosseini, Reza Mobasheri, Fabian L.Poletti, Judith A.Hoyland, Ali Mobasheri. (2016). Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods, 99, 69–80.
Rebekah M. Samsonraj, Michael Raghunath, Victor Nurcombe, James H. Hui, Andre j. Van Wijnen, Simon M. Cool. (2017). Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine. STEM CELLS Translational Medicine, 6(12), 2173-21. https://doi.org/10.1002/sctm.17-0129
Somayeh Keshtkar, Negar Azarpira, Mohammad Hossein Ghahremani, (2018) Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Research & Therapy, 9, 63. https://doi.org/10.1186/s13287-018-0791-7
Yao Fu, Lisanne Karbaat, Ling Wu, Jeroen Leijten, Sanne K. Both, Marcel Karperien. (2017). Trophic Effects of Mesenchymal Stem Cells in Tissue Regeneration. Tissue Engineering Part B: Reviews, 23(6), 515-528. https://doi.org/10.1089/ten.teb.2016.0365
Oryan, A., Kamali, A., Moshiri, A., Baghaban, E. M. (2017). Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence? Cell Tissue Organs, 204, 59-83. https://doi.org/10.1159/000469704.
Jun Guo, Guo-sheng Lin, Cui-yu Bao, Zhi-min Hu & Ming-yan Hu. (2007). Anti-Inflammation Role for Mesenchymal Stem Cells Transplantation in Myocardial Infarction. Inflammation, 30, 97–104. https://doi.org/10.1007/s10753-007-9025-3
Ugne Pivoraite, Akvile Jarmalaviciute, Virginijus Tunaitis, Giedre Ramanauskaite, Aida Vaitkuviene, Vytautas Kaseta, Gene Biziuleviciene, Algirdas Venalis, Augustas Pivoriunas. (2015). Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice. Inflammation, 38, 1933–1941. DOI: 10.1007/s10753-015-0173-6.
Leitner, D.R., Fruhbeck, G., Yumuk, V, et al. (2017). Obesity and Type 2 Diabetes: Two Diseases. with a Need for Combined Treatment Strategies – EASO Can Lead the Way. Obes Facts, 10(5), 483–492. doi: 10.1159/000480525.
Boloker, G., et al. Updated statistics of lung and bronchus cancer in United States. (2018). Journal of thoracic disease, 10(3), 1158–1161. doi:10.21037/jtd.2018.03.15.
Sitarz, R., et al. (2018). Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer management and research, 10, 239–248. doi: 10.2147/CMAR.S149619.
Petryk , N., Shevchenko O., (2020). Mesenchymal Stem Cells Anti-Inflammatory Activity in Rats: Proinflammatory Cytokines. J Inflamm Res, 13, 293–301. https://doi.org/10.2147/JIR.S256932
Petryk, N., Shevchenko, O. (2020). Anti-inflammatory Activity of Mesenchymal Stem Cells in λ-Carrageenan Induced Chronic Inflammation in Rats: Reactions of the Blood System, Leukocyte-Monocyte Ratio. Inflammation, 43, 1893–1901. https://doi.org/10.1007/s10753-020-01262-5
Klimenko, N. A., Tatarko, S. V., Shevchenko, A. N., Gubina-Vakulik, G. I. (2007). Justification of the model of chronic (secondary chronic) inflammation. Eksp. i clinich. medicine, 2, 24–28.
van der Meulen-Frank, M., Prins, J. B., Waarts, B. L., Hofstra, W. (2017). Vertebrate Animals Used for Experimental and Other Scientific Purposes: Principles and Practice for Legislation and Protection. In: Glaudemans, A., Medema, J., van Zanten, A., Dierckx, R., Ahaus, C. (eds). Quality in Nuclear Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-33531-5_5
Sproston , N.R., Ashworth , J.J. (2018). Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol, 9, 754. doi: 10.3389/fimmu.2018.00754.
Morrison, S. J., Scadden, D. T. (2014). The bone marrow niche for haematopoietic stem cells. Nature, 505(7483), 327–334. doi: 10.1038/nature12984.
Susanne Kern, Hermann Eichler, Johannes Stoeve, Harald Klüter, Karen Bieback (2012). Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue. Stem Cells, 24(5), 1294–1301. DOI: 10.1634/stemcells.2005-0342
Baldev, R. Gulati, R . K., Niharika, M., Pawan , K., Rajesh , K. , Somasundaram, Prem S. Yadav (2013). Bone Morphogenetic Protein-12 Induces Tenogenic Differentiation of Mesenchymal Stem Cells Derived from Equine Amniotic Fluid. Cells Tissues Organs, 198, 377–389. DOI: 10.1159/000358231.
Kassis, I., Zangi, L., Rivkin, R., Levdansky, L., Samuel, S., Marx, G., Gorodetsky, R. (2006). Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone. Marrow Transplant, 37(10), 967–76. PMID: 16670702. DOI: 10.1038/sj.bmt.1705358.
Uchida, K., Urabe, K., Naruse, K., Ujihira, M., Mabuchi, K., Itoman, M. (2007). Comparison of the cytokine-induced migratory response between primary and subcultured populations of rat mesenchymal bone marrow cells. J Orthop Sci, 12, 484–492. DOI 10.1007/s00776-007-1159-5.
Lee, J. S., et al. (2018). Reference values of neutrophil-lymphocyte ratio, lymphocytemonocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine, 97(26), e11138. doi: 10.1097/MD.0000000000011138.
Guo, Y-. H., et al. (2017). The clinical use of the platelet/lymphocyte ratio and lymphocyte/ monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis. Oncotarget , 8(12), 20011–20024. doi: 10.18632/oncotarget.15311.
Eo, Wan Kyu et al. (2016, ). The Lymphocyte-Monocyte Ratio Predicts Patient Survival and Aggressiveness of Ovarian Cancer. Journal of Cancer , 7(3), 289–96. doi:10.7150/jca.13432.
Ong, H. S., Gokavarapu, S., Wang, L. Z., Tian, Z., & Zhang, C. P. (2017). Low Pretreatment Lymphocyte-Monocyte Ratio and High Platelet-Lymphocyte Ratio Indicate Poor Cancer Outcome in Early Tongue Cancer. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 75(8), 1762–1774. https://doi.org/10.1016/j.joms.2016.12.023
Sierzega, M., Lenart, M., Rutkowska, M., et al. (2017). Preoperative Neutrophil-Lymphocyte and Lymphocyte-Monocyte Ratios Reflect Immune Cell Population Rearrangement in Resectable Pancreatic Cancer. Ann Surg Oncol 24, 808–815. https://doi.org/10.1245/s10434-016-5634-0 PMID: 27770341. PMCID: PMC5306070.
Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Yasuhito Iseki, Tetsuro Ikeya, Kosei Hirakawa. (2017). Prognostic significance of the preoperative lymphocyte to monocyte ratio in patients with colorectal cancer. Oncology Letters, 13, 1000–1006. DOI: 10.3892/ol.2016.5487.
Danielle Lux, Vafa Alakbarzade, Luke Bridge, Camilla N. Clark, Brian Clarke, Liqun Zhang, Usman Khan & Anthony C. Pereira. (2020). The association of neutrophil-lymphocyte ratio and lymphocytemonocyte ratio with 3-month clinical outcome after mechanical thrombectomy following stroke. Journal of Neuroinflammation, 17, art. No. 60. https://doi.org/10.1186/s12974-020-01739-y
Tekin, S., Avci, E., Nar, R., Degirmenci, E., Demir, S., & Senol, H. (2020). Are Monocyte/HDL, Lymphocyte/Monocyte and Neutrophil/Lymphocyte Ratios Prognostic or Follow-up Markers in Ischemic Cerebrovascular Patients? Journal of Basic and Clinical Health Sciences, 4(1), 38+. https://doi.org/10.30621/jbachs.2020.837.
Wang, Y., Chen, X., Cao, W. & Shi, Y. (2014). Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications . Nature Immunology, 15(11), 1009–1016.
Kean, T. J., Lin, P., Caplan, A. I. & Dennis, J. E. (2013). MSCs: delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells International, vol. 2013, Article ID 732742, 13 p.
Ren, G., Zhang, L., Zhao X., et al. (2008). Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell, 2(2), 141–150. doi: 10.1016/j.stem.2007.11.014. PMID: 18371435.
Anzalone, R., Iacono, M. L., Corrao, S., et al. (2010). New emerging potentials for human Wharton's jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity. Stem Cells and Development, 19(4), 423–438.
Abomaray, F. M., al Jumah, M. A., Alsaad, K. O., et al. (2016). Phenotypic and functional characterization of mesenchymal stem/multipotent stromal cells fromdecidua basalisof human term placenta. Stem Cells International, vol. 2016, Article ID 5184601, 18 p.
Nejati, M., Azami Tameh, A., Vahidinia, Z., Atlasi, M. A. (2018). Mesenchymal Stem Cells Improve Ischemic Stroke Injury by Anti-Inflammatory Properties in Rat Model of Middle Cerebral Artery Occlusion. Iran Red Crescent Med J, 20(1), e55085. doi: 10.5812/ircmj.55085.
Nejati, M., Tameh, A. A., Atlasi, M. A. (2014). Role of toll‐like receptors 2 and 4 in the neuroprotective effects of bone marrow-derived mesenchymal stem cells in an experimental model of ischemic stroke. J Cell Biochem, 120, 8053–8060. https://doi.org/10.1002/jcb.28083
Gao, F, Chi. u, S. M., Motan, D. A., et al. (2016). Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis, 7(1), e2062. doi: 10.1038/cddis.2015.327.
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