Keywords
autoimmunity
How to Cite
Abstract
A thorough investigation of the underlying immunopathogenetic pathways is required in order to create effective therapeutic methods for the complex clinical cases of patients with an autoreactive immune system that can harm the organism. Currently, the most commonly used therapeutic alternatives have severe side effects and reduced effectiveness after long-term treatment of patients with autoimmune diseases. The secretome of mesenchymal stem cells (MSCs-secretome) does, however, contain compounds with potential therapeutic applications, a promising new clinical strategy for treating the aforementioned patients. The data presented in this review summarizes information from experimental research and a small amount of clinical practice knowledge. It also raises fundamental questions regarding the role of modern, innovative therapies in helping autoimmune patients.
References
Bach JF. The hygiene hypothesis in autoimmunity: the role of pathogens and commensals. Nat Rev Immunol. 2018 Feb;18(2):105–20.
Margo CE, Harman LE. Autoimmune disease: Conceptual history and contributions of ocular immunology. Surv Ophthalmol. 2016 Oct;61(5):680–8.
Sieper J, Braun J, Rudwaleit M еt al. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002 Nov 1;61(suppl 3):iii8–18.
Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278(4):369–95.
Volkman HE, Stetson DB. The enemy within: endogenous retroelements and autoimmune disease. Nat Immunol. 2014 May;15(5):415–22.
Lodha M, Erhard F, Dölken L et al. The Hidden Enemy Within: Non-canonical Peptides in Virus-Induced Autoimmunity. Front Microbiol. 2022;13: 840911
Chandrashekara S. The treatment strategies of autoimmune disease may need a different approach from conventional protocol: A review. Indian J Pharmacol. 2012;44(6):665–71.
Neunert C, Farah R, Yacobovich J et al. Refractory autoimmune disease: an overview of when first-line therapy is not enough. Semin Hematol. 2016 Apr;53 Suppl 1:S35-38.
Aly RM. Current state of stem cell-based therapies: an overview. Stem Cell Investig. 2020 May 15;7:8.
Shah AA, Khan FA. Types and Classification of Stem Cells. In: Khan FA, editor. Advances in Application of Stem Cells: From Bench to Clinics. Springer International Publishing 2021; 25–49.
Lo B, Parham L. Ethical Issues in Stem Cell Research. Endocr Rev. 2009 May;30(3):204–13.
Beyer Nardi N, da Silva Meirelles L. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol. 2006;(174):249–82.
Merimi M, El-Majzoub R, Lagneaux L et al. The Therapeutic Potential of Mesenchymal Stromal Cells for Regenerative Medicine: Current Knowledge and Future Understandings. Front Cell Dev Biol. 2021;9.
Planat-Benard V, Varin A, Casteilla L. MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism. Front Immunol. 2021;12.
Műzes G, Sipos F. Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases. Cells. 2022 Jul 26;11(15):2300.
Desai MK, Brinton RD. Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan. Front Endocrinol. 2019;10.
Lazarus HM, Haynesworth SE, Gerson SL et al. Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant. 1995 Oct;16(4):557–64.
Mallis P, Michalopoulos E, Chatzistamatiou T et al. Interplay between mesenchymal stromal cells and immune system: clinical applications in immune-related diseases. Explor Immunol. 2021 Jun 30;1(2):112–39.
Kyurkchiev D, Bochev I, Ivanova-Todorova E et al. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells. 2014 Nov 26;6(5):552–70.
Caseiro AR, Pedrosa SS, Ivanova G et al. Mesenchymal Stem/ Stromal Cells metabolomic and bioactive factors profiles: A comparative analysis on the umbilical cord and dental pulp derived Stem/ Stromal Cells secretome. PLOS ONE. 2019 Nov 27;14(11):e0221378.
Alvites R, Branquinho M, Sousa AC et al. Mesenchymal Stem/Stromal Cells and Their Paracrine Activity-Immunomodulation Mechanisms and How to Influence the Therapeutic Potential. Pharmaceutics. 2022 Feb 9;14(2):381.
Alberts B, Johnson A, Lewis J et al. General Principles of Cell Communication. Mol Biol Cell 4th Ed. 2002;
Hindawi. Bioprocessing of Mesenchymal Stem Cells and Their Derivatives: Toward Cell-Free Therapeutics. 2018; 2018:9415367.
Li C, Zhao H, Cheng L, Wang B. Allogeneic vs. autologous mesenchymal stem/stromal cells in their medication practice. Cell Biosci. 2021 Nov 2;11(1):187.
Popis M, Konwerska A, Partyka M et al. Mesenchymal stem cells and their secretome - candidates for safe and effective therapy for systemic lupus erythematosus. Med J Cell Biol. 2021 Sep 1;9(3):110–22.
Cipriani P, Carubbi F, Liakouli V et al. Stem cells in autoimmune diseases: Implications for pathogenesis and future trends in therapy. Autoimmun Rev. 2013 May 1;12(7):709–16.
Kyurkchiev S, Kyurkchiev D. Mesenhymal stem cells - immunomodulatory activity and application. Central Medical Library, 2019; 220 p. ISBN 978-619-7491-03-6 TAURUS ADVERTISING EOOD
Moll G, Ankrum JA, Kamhieh-Milz J et al. Intravascular Mesenchymal Stromal/Stem Cell Therapy Product Diversification: Time for New Clinical Guidelines. Trends Mol Med. 2019 Feb;25(2):149–63.
Vizoso FJ, Eiro N, Cid S et al. Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine. Int J Mol Sci. 2017 Aug 25;18(9):E1852.
Braid LR, Wood CA, Wiese DM et al. Intramuscular administration potentiates extended dwell time of mesenchymal stromal cells compared to other routes. Cytotherapy. 2018 Feb;20(2):232–44.
L PK, Kandoi S, Misra R et al. The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine Growth Factor Rev. 2019 Apr;46:1–9.
Ahangar P, Mills SJ, Cowin AJ. Mesenchymal Stem Cell Secretome as an Emerging Cell-Free Alternative for Improving Wound Repair. Int J Mol Sci. 2020 Sep 24;21(19):E7038.
Gazdic M, Simovic Markovic B et al. Mesenchymal stem cells protect from acute liver injury by attenuating hepatotoxicity of liver natural killer T cells in an inducible nitric oxide synthase- and indoleamine 2,3-dioxygenase-dependent manner. J Tissue Eng Regen Med. 2018 Feb;12(2):e1173–85.
Milosavljevic N, Gazdic M, Simovic Markovic B et al. Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2017 Aug;23(8):1040–50.
Vasilev G, Goycheva MI, Ivanova-Todorova E et al. Conditioned Medium from Adipose Mesenchymal Stem Cell Exert Immunosuppressive Effect on Th17/Treg Axis in Rheumatoid Arthritis in Vitro. Ann Rheum Dis. 2019 Jun 1;78(Suppl 2):1074–5.
Gazdic M, Arsenijevic A, Markovic BS et al. Mesenchymal Stem Cell-Dependent Modulation of Liver Diseases. Int J Biol Sci. 2017 Sep 5;13(9):1109–17.
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005 Feb 15;105(4):1815–22.
Glennie S, Soeiro I, Dyson PJ et al. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood. 2005 Apr 1;105(7):2821–7.
Fan L, Hu C, Chen J et al. Interaction between Mesenchymal Stem Cells and B-Cells. Int J Mol Sci. 2016 May 5;17(5):650.
Peng Y, Chen X, Liu Q et al. Mesenchymal stromal cells infusions improve refractory chronic graft versus host disease through an increase of CD5+ regulatory B cells producing interleukin 10. Leukemia. 2015 Mar;29(3):636–46.
Gazdic M, Markovic BS, Arsenijevic A et al. Crosstalk between mesenchymal stem cells and T regulatory cells is crucially important for the attenuation of acute liver injury. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2018 May;24(5):687–702.
Bazzoni R, Takam Kamga P, Tanasi I et al. Extracellular Vesicle-Dependent Communication Between Mesenchymal Stromal Cells and Immune Effector Cells. Front Cell Dev Biol. 2020 Nov 6;8:596079.
Volarevic V, Gazdic M, Simovic Markovic B et al. Mesenchymal stem cell-derived factors: Immuno-modulatory effects and therapeutic potential. BioFactors Oxf Engl. 2017 Sep 10;43(5):633–44.
Shahir M, Mahmoud Hashemi S, Asadirad A et al. Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells. J Cell Physiol. 2020 Oct;235(10):7043–55.
Harrell CR, Volarevic V. Mesenchymal Stem Cell-Derived Secretome: A New Remedy for the Treatment of Autoimmune and Inflammatory Diseases. Stem Cells: Latest Advances. Springer International Publishing; 2021:59–69.
Wang J, Xia J, Huang R et al. Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization. Stem Cell Res Ther. 2020 Sep 29;11(1):424.
Xu H, Chen W, Zheng F et al. Reconstruction and analysis of the aberrant lncRNA–miRNA–mRNA network in systemic lupus erythematosus. Lupus. 2020 Apr 1;29(4):398–406.
Wang D, Huang S, Yuan X et al. The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus. Cell Mol Immunol. 2017 May;14(5):423–31.
Zhou T, Liao C, Li HY et al. Efficacy of mesenchymal stem cells in animal models of lupus nephritis: a meta-analysis. Stem Cell Res Ther. 2020 Feb 4;11(1):48.
Li W, Chen W, Sun L. An Update for Mesenchymal Stem Cell Therapy in Lupus Nephritis. Kidney Dis Basel Switz. 2021 Mar;7(2):79–89.
Perez-Hernandez J, Martinez-Arroyo O, Ortega A et al. Urinary exosomal miR-146a as a marker of albuminuria, activity changes and disease flares in lupus nephritis. J Nephrol. 2021 Aug 1;34(4):1157–67.
Perez-Hernandez J, Forner MJ, Pinto C et al. Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus. PLOS ONE. 2015 Sep 21;10(9):e0138618.
Chen L, Xiang B, Wang X, Xiang C. Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure. Stem Cell Res Ther. 2017 Jan 23;8(1):9.
Wu J, Lin S, Wan B, Velani B et al. Pyroptosis in Liver Disease: New Insights into Disease Mechanisms. Aging Dis. 2019 Oct;10(5):1094–108.
Shigemoto-Kuroda T, Oh JY, Kim D ki et al. MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis. Stem Cell Rep. 2017 May 9;8(5):1214–25.
Nakano M, Nagaishi K, Konari N et al. Bone marrow-derived mesenchymal stem cells improve diabetes-induced cognitive impairment by exosome transfer into damaged neurons and astrocytes. Sci Rep. 2016 Apr 22;6(1):24805.
Nojehdehi S, Soudi S, Hesampour A et al. Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type-1 autoimmune diabetes. J Cell Biochem. 2018;119(11):9433–43.
Chen Z, Wang H, Xia Y et al. Therapeutic Potential of Mesenchymal Cell–Derived miRNA-150-5p–Expressing Exosomes in Rheumatoid Arthritis Mediated by the Modulation of MMP14 and VEGF. J Immunol. 2018 Oct 15;201(8):2472–82.
Rui K, Hong Y, Zhu Q et al. Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells. Cell Mol Immunol. 2021 Feb;18(2):440–51.
Hai B, Shigemoto-Kuroda T, Zhao Q et al. Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren’s Syndrome. Stem Cells Int. 2018;2018: 2092315.
Wang G, Yuan J, Cai X et al. HucMSC-exosomes carrying miR-326 inhibit neddylation to relieve inflammatory bowel disease in mice. Clin Transl Med. 2020;10(2):e113.
Liu H, Liang Z, Wang F et al. Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism. JCI Insight [Internet]. 2020 May 13;4(24).
Yang S, Liang X, Song J et al. A novel therapeutic approach for inflammatory bowel disease by exosomes derived from human umbilical cord mesenchymal stem cells to repair intestinal barrier via TSG-6. Stem Cell Res Ther. 2021 May 29;12(1):315.
Qi LL, Fan ZY, Mao HG et al. The Therapeutic Efficacy of Adipose Tissue-Derived Mesenchymal Stem Cell Conditioned Medium on Experimental Colitis Was Improved by the Serum From Colitis Rats. Front Bioeng Biotechnol. 2021;9:694908.
Seetharaman R, Mahmood A, Kshatriya P et al. Mesenchymal Stem Cell Conditioned Media Ameliorate Psoriasis Vulgaris: A Case Study. Case Rep Dermatol Med. 2019;2019:8309103.
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