MSC-CM and its potential for autoimmune diseases treatments

Autoimmune diseases, also known as autoimmune disorders, are conditions where the body’s immune system mistakenly reacts and attacks its own cells and tissues as if they were foreign objects. As a result, autoimmune diseases can occur in any part of the body, leading to various symptoms. Some common autoimmune diseases include lupus, rheumatoid arthritis, inflammatory bowel disease, autoimmune hemolytic anemia, autoimmune thyroid disease, and Graves’ disease. Scientists have not fully understood the exact causes of autoimmune diseases (1). Stem cells have the ability to turn into the cells of damaged organs when they touch the damaged organs, and that being the case, they are used in the treatment of autoimmune diseases.

Autoimmune diseases rank third in global danger levels, following cardiovascular diseases and cancer. Treatment methods for autoimmune diseases often focus on managing symptoms and supporting the immune system (2). These diseases often pose a challenge for complete treatment, significantly affecting daily life activities, and if left untreated, they can cause severe complications that cause disability or death (2). According to the Centers for Disease Control and Prevention (CDC) statistics, about 8% of the US population is affected by autoimmune diseases, with 78% being women, significantly impacting their work and daily lives (3).

Characteristics of MSC-CM

The most potential alternative treatment methods currently include stem cell therapy. Mesenchymal stem cells (MSC) can self-renew and differentiate into various cell lineages (4). MSCs regulate immune system functions, including T-cell proliferation, B-cell modulation, antigen-presenting cell maturation, and promotion of anti-inflammatory processes (4) (5). Alongside cell therapy, the use of conditioned media (CM) containing bioactive factors secreted by MSCs is actively developing. MSCs actively secrete intermediate substances like proteins, peptides, RNA, and lipids (6), and researchers can concentrate and freeze-dry these substances without losing their activity. It presents a significant advantage over cell therapy, which requires storage in deep nitrogen conditions and good infrastructure for freezing cell banks (7), reducing costs and minimizing the recipient’s graft rejection.

Figure 1: Application of MSC-CM in autoimmune diseases (5)

MSC-CM participates in the treatment/ support of autoimmune diseases

The component secreted by MSCs, extracellular vesicles, has been effective in treating some immune-related diseases and low-grade joint diseases, including multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, osteoporosis, systemic lupus erythematosus, Sjogren’s syndrome, and other autoimmune diseases (Figure 1) (5). In 2019, a research group at Saint-Eloi Hospital, Montpellier, France, demonstrated that secretion from cultured MSCs (MSC-CM) helped reduce clinical signs of inflammation, showing significant potential in treating joint inflammation(8). The research team showed its effectiveness in a mouse model, revealing MSC-CM’s efficacy in immune regulation to prevent inflammation. In that year in India, the research team successfully treated a 38-year-old male patient who had severe psoriasis for two years using MSC-secreted substances (Figure 2). Remarkably, the patient fully recovered after just one month of treatment (with a PSSI score dropping from 28 to 0) (9).

Mechanistically, the treatment’s effectiveness might be because of MSC-CM containing many biological agents, such as prostaglandin E2 (PGE2) and transforming growth factor β1 (TGF-β1) related to immune regulation, hepatocyte growth factor (HGF), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF), and angiopoietin-1 (ANG-1) (10). Through these factors, MSC-CM can inhibit the expression of the chemokine CXC (CXCL) 1 and regulate the reduction of IL-17A and IL-22 production from γδ T cells. Additionally, MSC-CM may inhibit the secretion of IL-8 from dermal epithelial cells stimulated by IFN-γ and TNF-α (10). These promising results affirm that MSC-CM could be a highly effective method for overcoming the limitations of conventional cell therapy. However, researchers have currently published limited comprehensive clinical trial reports on the use of MSC-CM in autoimmune disease treatment.

Figure 2: Images of a psoriasis patient before and after treatment with MSC-CM (9)

Therefore, MSC-CM holds great promise in treating autoimmune diseases. Further in-depth research in this field is being notably emphasized by scientists worldwide to verify safety, effectiveness and standardize production.

References

1. Recent advances in the genetics of autoimmune disease . Gregersen PK, Olsson LM. doi: 10.1146/annurev.immunol.021908.132653., s.l. : Annu Rev Immunol, 2009, Vols. 27:363-91.
2. The treatment strategies of autoimmune disease may need a different approach from conventional protocol: a review. S, Chandrashekara. doi: 10.4103/0253-7613.103235, s.l. : Indian J Pharmacol, 2012, Vols. 44(6):665-71.
3. Women and Autoimmune Diseases. Fairweather, D., & Rose, N. R. s.l. : Emerging Infectious Diseases, 2004.
4. Mesenchymal stem cell differentiation and roles in regenerative medicine. Hwang NS, Zhang C, Hwang YS, Varghese S. doi: 10.1002/wsbm.26. PMID: 20835984., s.l. : Wiley Interdiscip Rev Syst Biol Med., 2009, Vols. 1(1):97-106. .
5. Application of extracellular vesicles derived from mesenchymal stem cells as potential therapeutic tools in autoimmune and rheumatic diseases. Huldani, H., Jasim, S. A., Bokov, D. O., Abdelbasset, W. K., Shalaby, M. N., Thangavelu, L., … & Qasim, M. T. International Immunopharmacology, 106, 108634 2022.
6. Role of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in ligament or tendon healing: A Systematic Review from 1998-2018. Rhatomy S, Sumarwoto T, Prijosedjati A, Romaniyanto , Prasetyo TE. doi: 10.1177/2325967120S00109., s.l. : Orthop J Sports Med., 2020.
7. In vitro study of the mesenchymal stem cells-conditional media role in skin wound healing process: A systematic review. Heydari MB, Ghanbari-Movahed Z, Heydari M, Farzaei MH. doi: 10.1111/iwj.13796. , s.l. : Int Wound J. , 2022, Vols. 19(8):2210-2223.
8. Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis. Cosenza S, Toupet K, Maumus M, Luz-Crawford P, Blanc-Brude O, Jorgensen C, Noël D. doi: 10.7150/thno, s.l. : Theranostics, 2018, Vols. 8(5):1399-1410.
9. Mesenchymal Stem Cell Conditioned Media Ameliorate Psoriasis Vulgaris: A Case Study. Rajasekar Seetharaman, Anjum Mahmood, Prashant Kshatriya, Divyang Patel, Anand Srivastava. https://doi.org/10.1155/2019/8309103, s.l. : Case Reports in Dermatological Medicine, 2019, Vols. vol. 2019, Article ID 8309103, 5 pages.
10. The therapeutic applications of mesenchymal stromal cells from human perinatal tissues in autoimmune diseases. Yang, C., M. Wu, M. You, Y. Chen, M. Luo, and Q. Chen. s.l. : Stem Cell Research & Therapy, 2021, Vols. 12(1): p. 103, 10.1186/s13287-021-02158-3.