rheumatoid arthritis
juvenile idiopathic arthritis
mesenchymal stem cell

How to Cite

Margareta, F., Nugraha, Y., Nurcita, B., & Fauziah, C. (2022). POTENTIAL OF UMBILICAL CORD MESENCHYMAL STEM CELL (UC-MSC) IN THERAPY OF RHEUMATOID ARTHRITIS (RA). Rheumatology (Bulgaria), 30(2), 44-52. https://doi.org/10.35465/30.2.2022.pp44-52


Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of the joints. Even RA usually found in elderly patients, however, it is possible to occur at a young age, such as juvenile rheumatoid arthritis (JRA), the most common type of arthritis in children and adolescents. Unfortunately, common conventional therapies given to patients with RA to modulate the immune response, including disease-modifying anti-rheumatic drugs (DMARDS) and nonsteroidal anti-inflammatory drugs (NSAIDs), found have limitation therapeutic effects in RA patients. Long-term use of these drugs will cause side effects and resistance to therapy. In recent years mesenchymal stem cells (MSCs) are highly recommended therapy. The therapy considered promising for curative action in RA patient due to potential as immunomodulators that MSCs can differentiate into various cell types and stimulate tissue repair. These cells also have strong chemotactic abilities because they can migrate to damaged tissues and act as an anti-inflammatory. Therefore, MSC potentially suitable for autoimmune therapy. In addition, many research evidences in clinical trials stating that there are no toxicity and side effects in the long term. One type of MSC based on its tissue source is umbilical cord mesenchymal stem cell which is believed to be the best among other types. This review discusses a UC-MSC-based therapeutic approach in children, adults, and the elderly focusing based on published clinical data and clinical trials for the treatment of RA that are currently ongoing.



  1. C.-X. Lv, H. Duan, S. Wang, L. Gan, and Q. Xu, “Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Promote Proliferation of Allogeneic Endometrial Stromal Cells,” Reprod. Sci., vol. 27, no. 6, pp. 1372–1381, 2020, doi: 10.1007/s43032-020-00165-y.
  2. Kasper, Fauci, Hauser, Longo, Jameson, and Loscalzo, Harrison’s Principles Internal Medicine 19th edition. New York ;Chicago; San Francisco; Athens; London; Madrid; Mexico City, 2014.
  3. F. Fia and J. Westra, “Overview of rheumatoid arthritis therapy: Management options in Indonesia,” Tarumanagara Med. J., vol. 1, no. 1, pp. 208–220, 2018, doi: 10.24912/tmj.v1i1.2524.
  4. F. Luis and G. Moncayo, Apley and Solomon’s System of Orthopaedics and Trauma tenth edition. boca raton london new york: Taylor and Francis Group, 2018.
  5. M. Lopez-Santalla, R. Fernandez-Perez, and M. I. Garin, “Mesenchymal stem/stromal cells for rheumatoid arthritis treatment: an update on clinical applications,” cells, pp. 1–21, 2020, doi: 10.3390/cells9081852.
  6. I. Ullah, R. B. Subbarao, and G. J. GJ Rho, “Human mesenchymal stem cells-current trends and future prospective,” Biosci. Rep., vol. 35, p. 191, 2015, doi: 10.1042/BSR20150025.
  7. Y. Sun, W. Deng, L. Geng, L. Zhang, and … R. L., “Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting Th17 cells,” J. Immunol., pp. 1–13, 2015, doi: 10.1155/2015/284215.
  8. G. Vasilev, E. Krasimirova, M. Ivanova, R. Gancheva, R. Stoilov, and D. Kyurkchiev, “Effects Exerted By Mesenchymal Stem Cells On Monocytes Obtained From Patients With Rheumatoid Arthritis And Progressive Systemic Sclerosis Мск от години попадат в полезрението и широко се дискутира потенциалното им приложение като средство за терапевтично,” Rheumatology, vol. XXVII, no. 3, pp. 44–54, 2019, doi: 10.35465/27.3.2019.pp44-54.
  9. E. E. A. Arts, J. Fransen, A. A. Den Broeder, P. L. C. M. Van Riel, and C. D. Popa, “Low disease activity (DAS28≤3.2) reduces the risk of first cardiovascular event in rheumatoid arthritis: A time-dependent Cox regression analysis in a large cohort study,” Ann. Rheum. Dis., vol. 76, no. 10, pp. 1693–1699, Oct. 2017, doi: 10.1136/annrheumdis-2016-210997.
  10. G. S. Bilotta, A. M. Milner, and I. L. Boyd, “Quality assessment tools for evidence from environmental science,” Environ. Evid., vol. 3, no. 1, Sep. 2014, doi: 10.1186/2047-2382-3-14.
  11. N. Choudhary, L. K. Bhatt, and K. S. Prabhavalkar, “Experimental animal models for rheumatoid arthritis,” Immunopharmacol. Immunotoxicol., vol. 40, no. 3, pp. 193–200, May 2018, doi: 10.1080/08923973.2018.1434793.
  12. C. Almeida et al., “Biologic interventions for fatigue in rheumatoid arthritis,” Cochrane database Syst. Rev., no. 6, p. CD008334, 2016, doi: 10.1002/14651858.CD008334.PUB2.
  13. S. Shen, T. O’Brien, L. M. Yap, H. M. Prince, and C. J. McCormack, “The use of methotrexate in dermatology: A review,” Australas. J. Dermatol., vol. 53, no. 1, pp. 1–18, 2012, doi: 10.1111/J.1440-0960.2011.00839.X.
  14. N. Luque-Campos et al., “Mesenchymal stem cells improve rheumatoid arthritis progression by controlling memory T cell response,” Front. Immunol., vol. 10, no. MAR, 2019, doi: 10.3389/FIMMU.2019.00798/FULL.
  15. G. Temiz, S. Kemmner, and U. Heemann, “Graft Versus Host Disease,” Onco-Nephrology, Oct. 15, 2021. https://www.ncbi.nlm.nih.gov/books/NBK538235/ (accessed Apr. 12, 2022).
  16. T. Li, M. Xia, Y. Gao, Y. Chen, and Y. Xu, “Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy,” Expert Opin Biol Ther. 2015;15(9):1293-306. http://dx.doi.org/10.1517/14712598.2015.1051528, vol. 15, no. 9, pp. 1293–1306, Sep. 2015, doi: 10.1517/14712598.2015.1051528.
  17. I. M. . Hansen, R. . Andreasen, M. N. van Bui Hansen, and A. Emamifar, “The reliability of disease activity score in 28 joints–C-reactive protein might be overestimated in a subgroup of rheumatoid arthritis patients, when the score is solely based on subjective parameters: a cross-sectional, exploratory study,” J. Clin. Rheumatol., pp. 102–106, 2017, doi: 10.1097/RHU.0000000000000469.
  18. A. Karamini, A. Bakopoulou, D. Andreadis, K. Gkiouras, and A. Kritis, “Therapeutic potential of mesenchymal stromal stem cells in rheumatoid arthritis: a systematic review of in vivo studies,” Stem Cell Rev Rep, vol. 16, no. 2, pp. 276–287, Apr. 2015, doi: 10.1007/s12015-020-09954-z.
  19. X. Xu et al., “Combination of human umbilical cord mesenchymal stem (stromal) cell transplantation with IFN-γ treatment synergistically improves the clinical outcomes of patients with rheumatoid arthritis,” Ann. Rheum. Dis., vol. 79, no. 10, pp. 1298–1304, Oct. 2020, doi: 10.1136/ANNRHEUMDIS-2020-217798.
  20. Y. Yang et al., “Serum IFN-γ levels predict the therapeutic effect of mesenchymal stem cell transplantation in active rheumatoid arthritis,” J. Transl. Med., vol. 16, no. 1, pp. 1–9, Jun. 2018, doi: 10.1186/S12967-018-1541-4/FIGURES/5.
  21. E. Park, H. Lim, S. Lee, K. Roh, and … K. S., “Intravenous infusion of umbilical cord blood-derived mesenchymal stem cells in rheumatoid arthritis: a phase Ia clinical trial,” Stem Cells Transl. Med., pp. 1–7, 2018, doi: 10.1002/sctm.18-0031.
  22. S. Ma, N. Xie, W. Li, B. Yuan, and Y. Shi, “Immunobiology of mesenchymal stem cells,” Cell Death Differ., pp. 216–225, 2014, doi: 10.1038/cdd.2013.158.
  23. T. Qi, H. Gao, Y. Dang, and S. Huang, “Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis,” Medicine (Baltimore)., pp. 1–6, 2020, doi: 10.1097/MD.0000000000021222.
  24. H. Almoallim et al., “A Review of the Prevalence and Unmet Needs in the Management of Rheumatoid Arthritis in Africa and the Middle East,” Rheumatol. Ther., vol. 8, no. 1, Mar. 2021, doi: 10.1007/S40744-020-00252-1.
  25. A. I. Caplan, “Mesenchymal Stem Cells in Regenerative Medicine,” Princ. Regen. Med., pp. 219–227, Jan. 2019, doi: 10.1016/B978-0-12-809880-6.00015-1.
  26. Daryanti, B. Widiyanto, and Sudirman, “Literature Review : Faktor Yang Berhubungan Dengan Rheumatoid Artritis Pada Lansia,” Nurs. Arts, vol. 14, no. 1, pp. 7–12, Jun. 2020, doi: 10.36741/JNA.V14I1.103.
  27. D. C. Ding, Y. H. Chang, W. C. Shyu, and S. Z. Lin, “Human umbilical cord mesenchymal stem cells: A new era for stem cell therapy,” Cell Transplant., vol. 24, no. 3, pp. 339–347, 2015, doi: 10.3727/096368915X686841.
  28. S. A. Fazal et al., “A clinical update and global economic burden of rheumatoid arthritis,” Endocrine, Metab. Immune Disord. Targets, vol. 18, pp. 98–109, 2018, doi: 10.2174/1871530317666171114122417.
  29. V. Gouveia, S. Lima, C. Nunes, and S. Reis, “Non-biologic nanodelivery therapies for rheumatoid arthritis,” J. Biomed. Nanotechnol., vol. 11, no. 10, pp. 1701–1721, 2015, doi: 10.1166/jbn.2015.2159.
  30. Y. F. Han, R. Tao, T. J. Sun, J. K. Chai, G. Xu, and J. Liu, “Optimization of human umbilical cord mesenchymal stem cell isolation and culture methods,” Cytotechnology, vol. 65, no. 5, pp. 819–827, Oct. 2013, doi: 10.1007/S10616-012-9528-0.
  31. R. Hansildaar, D. Vedder, M. Baniaamam, A. K. Tausche, M. Gerritsen, and M. T. Nurmohamed, “Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout,” Lancet Rheumatol., vol. 3, no. 1, pp. e58–e70, 2021, doi: 10.1016/S2665-9913(20)30221-6.
  32. T. S. Hariyati, “Mengenal systematic review theory dan studi kasus,” J. Keperawatan Indones., pp. 124–132, 2010, doi: 10.7454/jki.v13i2.242.
  33. J. Kay and K. S. KS Upchurch, “ACR/EULAR 2010 rheumatoid arthritis classification criteria,” Rheumatology, vol. 51, no. 6, pp. vi5–vi9, 2012, doi: 10.1093/rheumatology/kes279.
  34. P. Lazzerini, P. L. Capecchi, and F. Laghi-Pasini, “Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis,” Eur. Heart J., vol. 38, no. 22, pp. 1717–1727, 2017, doi: 10.1093/eurheartj/ehw208.
  35. M. Maqsood, M. Kang, X. Wu, J. Chen, L. Teng, and L. Qiu, “Adult mesenchymal stem cells and their exosomes: Sources, characteristics, and application in regenerative medicine,” Life Sci. 256, pp. 1–9, 2020, doi: 10.1016/j.lfs.2020.118002.
  36. I. McInnes and G. Schett, “Pathogenetic insights from the treatment of rheumatoid arthritis,” Lancet, vol. 389, no. 10086, pp. 2328–2337, 2017, doi: 10.1016/S0140-6736(17)31472-1.
  37. M. J. Page et al., “The PRISMA 2020 statement: an updated guideline for reporting systematic reviews,” BMJ, vol. 372, Mar. 2021, doi: 10.1136/BMJ.N71.
  38. A. Naji, M. Eitoku, B. Favier, F. Deschaseaux, N. Rouas-Freiss, and N. Suganuma, “Biological functions of mesenchymal stem cells and clinical implications,” Cell. Mol. Life Sci., vol. 76, no. 17, pp. 3323–3348, Sep. 2019, doi: 10.1007/S00018-019-03125-1.
  39. A. A. Nargesi, L. O. Lerman, and A. Eirin, “Mesenchymal stem cell-derived extracellular vesicles for kidney repair: Current status and looming challenges,” Stem Cell Res. Ther., vol. 8, no. 1, pp. 1–12, Dec. 2017, doi: 10.1186/S13287-017-0727-7.
  40. T. Ohno, D. Aune, and A. K. Heath, “Adiposity and the risk of rheumatoid arthritis: a systematic review and meta-analysis of cohort studies,” Sci. Rep., vol. 10, no. 1, pp. 1–12, 2020, doi: 10.1038/s41598-020-71676-6.
  41. A. I. Prasetio and T. Wijayanto, “Literature Review Aplikasi Indeks Penyakit Pasien Rawat Jalan,” Adm. Heal. Inf. J., vol. 2, no. 1, pp. 10–14, 2021, Accessed: Apr. 12, 2022. [Online]. Available: http://ojs.stikeslandbouw.ac.id/index.php/ahi/article/download/168/132
  42. L. Schmidt, B. K. Olorisade, L. A. McGuinness, J. Thomas, and J. P. T. Higgins, “Data extraction methods for systematic review (semi)automation: A living systematic review,” F1000Research, vol. 10, no. 401, pp. 1–35, 2021, doi: 10.12688/F1000RESEARCH.51117.1/DOI.
  43. M. Timaner, K. Tsai, and Y. Shaked, “The multifaceted role of mesenchymal stem cells in cancer,” Semin. cancer Biol., vol. 60, pp. 225–237, 2020, doi: 10.1016/j.semcancer.2019.06.003.
  44. C. Tufanaru, Z. Munn, E. Aromataris, J. Campbell, and L. Hopp, “Chapter 3: Systematic Reviews of Effectiveness,” JBI Manual for Evidence Synthesis, 2020. https://synthesismanual.jbi.global (accessed Apr. 12, 2022).
  45. L. Wang et al., “Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study,” Drug Des. Devel. Ther., vol. 13, p. 4331, 2019, doi: 10.2147/DDDT.S225613.
  46. L. Wang et al., “Clinical observation of employment of umbilical cord derived mesenchymal stem cell for juvenile idiopathic arthritis therapy,” Stem Cells Int., vol. 2016, pp. 1–8, 2016, doi: 10.1155/2016/9165267.
  47. Z. Yu, F. Reynaud, M. Lorscheider, N. Tsapis, and E. Fattal, “Nanomedicines for the delivery of glucocorticoids and nucleic acids as potential alternatives in the treatment of rheumatoid arthritis,” Wiley Interdiscip. Rev. Nanomedicine Nanobiotechnology, vol. 12, no. 5, p. e1630, Sep. 2020, doi: 10.1002/WNAN.1630.
  48. L. Wang et al., “Human Umbilical Cord Mesenchymal Stem Cell Therapy for Patients with Active Rheumatoid Arthritis: Safety and Efficacy,” Stem Cell Dev., vol. 22, no. 24, pp. 3192–3202, Aug. 2013, doi: 10.1089/SCD.2013.0023.
  49. K. Chauhan, J. S. Jandu, A. Goyal, and M. A. Al-Dhahir, “Rheumatoid Arthritis,” Rosen Barkin’s 5-Minute Emerg. Med. Consult Fifth Ed., Oct. 2021, doi: 10.1017/chol9780521332866.074.
  50. Indonesian Rheumatology Association, Diagnosis & Penatalaksanaan Artritis Reumatoid – Perhimpunan Reumatologi Indonesia. 2014. [Online]. Available: https://reumatologi.or.id/rekomendasi-perhimpunan-reumatologi-indonesia-reumatoid-artritis-2014/
  51. R. Hidayat et al., Diagnosis dan Pengelolaan Artritis Reumatoid (Rheumatoid Arthritis Diagnosis and Management). 2021. [Online]. Available: https://reumatologi.or.id/wp-content/uploads/2021/04/Rekomendasi-RA-Diagnosis-dan-Pengelolaan-Artritis-Reumatoid.pdf
  52. S. Moola et al., “Chapter 7: Systematic Reviews of Etiology and Risk,” JBI Man. Evid. Synth., 2020, doi: 10.46658/JBIMES-20-08.
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