Adusumilli Pramod Kumar 1, Jeesa George 1
1 Department of Pharmacy Practice, Faculty of Pharmacy, Ramaiah University of Applied Sciences, Gnanagangothri Campus, Bangalore-560054, India.
Abstract
Immunosuppressive drugs are substances that suppress or reduce the strength of the body's immune system. They are often used to manage conditions where an overactive immune response leads to tissue damage or disease progression. Mesenchymal Stem Cells (MSCs) have garnered significant attention in research due to their multifaceted immunological properties, presenting them as potential therapeutic candidates for a range of disorders, including autoimmune diseases and tumors. Initially recognized for their ability to suppress T lymphocytes, recent studies have highlighted MSCs' impact on various immune cell types, T cells, B cells, natural killer (NK) cells, dendritic cells (DCs), macrophages, and neutrophils, underscoring their complex role in immune regulation and tolerance development. MSCs primarily suppress the immune system by inhibiting T cell proliferation through the release of substances such as TGF-β, HGF, PGE2, IL-10, HLA-G5, and IDO, promoting the generation of regulatory T cells (Tregs) that further dampen immune reactions. Furthermore, MSCs influence the function of DCs by impeding their development and maturation processes, while also enhancing the production of inflammatory molecules like IL-10. Similarly, MSCs hinder the proliferation of B cells and their antibody production, particularly in inflammatory contexts. Thus, immunosuppressive potential of MSCs holds significant promise for therapeutic applications.
Keywords: Immunosuppression, MSC, Medicine, Immunomodulation, Immune cells.
References
[1] Y. Hussain y H. Khan, «Immunosuppressive Drugs», Encycl. Infect. Immun., pp. 726-740, 2022, doi: 10.1016/B978-0-12-818731-9.00068-9.
[2] M. Suthanthiran, R. E. Morris, y T. B. Strom, «Immunosuppressants: Cellular and molecular mechanisms of action», Am. J. Kidney Dis., vol. 28, n.o 2, pp. 159-172, ago. 1996, doi: 10.1016/S0272-6386(96)90297-8.
[3] D. D. Kanatoula, E. Bodner, K. Ghoreschi, K. Meier, y F. Solimani, «Non-biologic immunosuppressive drugs for inflammatory and autoimmune skin diseases», JDDG J. Dtsch. Dermatol. Ges., vol. 22, n.o 3, pp. 400-421, 2024, doi: 10.1111/ddg.15270.
[4] M. E. Bernardo, F. Locatelli, y W. E. Fibbe, «Mesenchymal stromal cells», Ann. N. Y. Acad. Sci., vol. 1176, pp. 101-117, sep. 2009, doi: 10.1111/j.1749-6632.2009.04607.x.
[5] N. Song, M. Scholtemeijer, y K. Shah, «Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic potential», Trends Pharmacol. Sci., vol. 41, n.o 9, pp. 653-664, sep. 2020, doi: 10.1016/j.tips.2020.06.009.
[6] M. Krampera et al., «Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide», Blood, vol. 101, n.o 9, pp. 3722-3729, may 2003, doi: 10.1182/blood-2002-07-2104.
[7] H. Afkhami, G. Mahmoudvand, A. Fakouri, A. Shadab, M. Mahjoor, y T. Komeili Movahhed, «New insights in application of mesenchymal stem cells therapy in tumor microenvironment: pros and cons», Front. Cell Dev. Biol., vol. 11, p. 1255697, oct. 2023, doi: 10.3389/fcell.2023.1255697.
[8] G. O’Malley et al., «Mesenchymal stromal cells (MSCs) and colorectal cancer: a troublesome twosome for the anti-tumour immune response?», Oncotarget, vol. 7, n.o 37, pp. 60752-60774, ago. 2016, doi: 10.18632/oncotarget.11354.
[9] N. Negi y M. D. Griffin, «Effects of mesenchymal stromal cells on regulatory T cells: Current understanding and clinical relevance», Stem Cells Dayt. Ohio, vol. 38, n.o 5, pp. 596-605, may 2020, doi: 10.1002/stem.3151.
[10] D. M. Darlan, A. Raga, A. M. Muhar, A. Putra, y I. Alif, «Mesenchymal Stem Cells Suppress Dendritic Cells and Modulate Proinflammatory Milieu Through Interleukin-10 Expression in Peripheral Blood Mononuclear Cells of Human Systemic Lupus Erythematosus», Acta Inform. Medica, vol. 31, n.o 1, pp. 20-25, mar. 2023, doi: 10.5455/aim.2023.31.20-25.
[11] N. Luque-Campos et al., «The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming», Front. Immunol., vol. 12, p. 624746, jun. 2021, doi: 10.3389/fimmu.2021.624746.
[12] A. Bartholomew et al., «Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo», Exp. Hematol., vol. 30, n.o 1, pp. 42-48, ene. 2002, doi: 10.1016/s0301-472x(01)00769-x.
[13] M. Di Nicola et al., «Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli», Blood, vol. 99, n.o 10, pp. 3838-3843, may 2002, doi: 10.1182/blood.v99.10.3838.
[14] F. Djouad et al., «Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals», Blood, vol. 102, n.o 10, pp. 3837-3844, nov. 2003, doi: 10.1182/blood-2003-04-1193.
[15] S. Zheng et al., «Mesenchymal Stromal Cells Rapidly Suppress TCR Signaling-Mediated Cytokine Transcription in Activated T Cells Through the ICAM-1/CD43 Interaction», Front. Immunol., vol. 12, p. 609544, feb. 2021, doi: 10.3389/fimmu.2021.609544.
[16] J. Plumas, L. Chaperot, M.-J. Richard, J.-P. Molens, J.-C. Bensa, y M.-C. Favrot, «Mesenchymal stem cells induce apoptosis of activated T cells», Leukemia, vol. 19, n.o 9, pp. 1597-1604, sep. 2005, doi: 10.1038/sj.leu.2403871.
[17] P. A. Sotiropoulou, S. A. Perez, A. D. Gritzapis, C. N. Baxevanis, y M. Papamichail, «Interactions between human mesenchymal stem cells and natural killer cells», Stem Cells Dayt. Ohio, vol. 24, n.o 1, pp. 74-85, ene. 2006, doi: 10.1634/stemcells.2004-0359.
[18] C. de V. Machado, P. D. da S. Telles, y I. L. O. Nascimento, «Immunological characteristics of mesenchymal stem cells», Rev. Bras. Hematol. E Hemoter., vol. 35, n.o 1, pp. 62-67, 2013, doi: 10.5581/1516-8484.20130017.
[19] S. Glennie, I. Soeiro, P. J. Dyson, E. W.-F. Lam, y F. Dazzi, «Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells», Blood, vol. 105, n.o 7, pp. 2821-2827, abr. 2005, doi: 10.1182/blood-2004-09-3696.
[20] A. Corcione et al., «Human mesenchymal stem cells modulate B-cell functions», Blood, vol. 107, n.o 1, pp. 367-372, ene. 2006, doi: 10.1182/blood-2005-07-2657.
[21] X.-X. Jiang et al., «Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells», Blood, vol. 105, n.o 10, pp. 4120-4126, may 2005, doi: 10.1182/blood-2004-02-0586.
[22] G. M. Spaggiari, A. Capobianco, S. Becchetti, M. C. Mingari, y L. Moretta, «Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation», Blood, vol. 107, n.o 4, pp. 1484-1490, feb. 2006, doi: 10.1182/blood-2005-07-2775.
[23] J. Tolar, K. Le Blanc, A. Keating, y B. R. Blazar, «Hitting the right spot with mesenchymal stromal cells (MSCs)», Stem Cells Dayt. Ohio, vol. 28, n.o 8, pp. 1446-1455, ago. 2010, doi: 10.1002/stem.459.
[24] Y. Jiang et al., «Mesenchymal stem cell-derived exosomes can alleviate GVHD and preserve the GVL effect in allogeneic stem cell transplantation animal models», Front. Immunol., vol. 14, p. 1284936, 2023, doi: 10.3389/fimmu.2023.1284936.
[25] O. N. Koç et al., «Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy», J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol., vol. 18, n.o 2, pp. 307-316, ene. 2000, doi: 10.1200/JCO.2000.18.2.307.
[26] M. E. Bernardo et al., «Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation», Bone Marrow Transplant., vol. 46, n.o 2, pp. 200-207, feb. 2011, doi: 10.1038/bmt.2010.87.
[27] J. A. Snowden et al., «Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR», J. Rheumatol., vol. 31, n.o 3, pp. 482-488, mar. 2004.
[28] J. Moore et al., «A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis», Arthritis Rheum., vol. 46, n.o 9, pp. 2301-2309, sep. 2002, doi: 10.1002/art.10495.
[29] Ö. Satirer, J. C. Henes, M. Döring, T. Lesk, S. Benseler, y J. B. Kuemmerle-Deschner, «Autologous haematopoiesis stem cell transplantation (AHSCT) for treatment-refractory autoimmune diseases in children», RMD Open, vol. 10, n.o 3, p. e004381, jul. 2024, doi: 10.1136/rmdopen-2024-004381.
[30] S. Goklemez et al., «Long-term follow-up after lymphodepleting autologous haematopoietic cell transplantation for treatment-resistant systemic lupus erythematosus», Rheumatol. Oxf. Engl., vol. 61, n.o 8, pp. 3317-3328, dic. 2021, doi: 10.1093/rheumatology/keab877.
[31] E. J. Dozois et al., «Durable Response in Patients With Refractory Fistulizing Perianal Crohn’s Disease Using Autologous Mesenchymal Stem Cells on a Dissolvable Matrix: Results from the Phase I Stem Cell on Matrix Plug Trial», Dis. Colon Rectum, vol. 66, n.o 2, pp. 243-252, feb. 2023, doi: 10.1097/DCR.0000000000002579.
[32] X.-X. Wan et al., «Stem Cell Transplantation in the Treatment of Type 1 Diabetes Mellitus: From Insulin Replacement to Beta-Cell Replacement», Front. Endocrinol., vol. 13, p. 859638, mar. 2022, doi: 10.3389/fendo.2022.859638.
Publication