The Role of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC) in Rheumatoid Arthritis: A Literature Review and Bibliographic Study
DOI:
https://doi.org/10.35451/6mrp2h76Keywords:
UC-MSC, Rheumatoid Arthritis, Immunomodulation, TregAbstract
Umbilical Cord-derived Mesenchymal Stem Cells (UC-MSCs) are promising candidates for innovative therapy in rheumatoid arthritis (RA) due to their immunomodulatory and regenerative properties. RA is a chronic autoimmune disease characterized by persistent synovial inflammation, progressive joint destruction, and immune dysregulation involving T cells, B cells, and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. This study aims to analyze the research development and therapeutic potential of UC-MSCs in RA through a bibliometric approach and literature review. Data were collected from PubMed, Dimensions, ScienceDirect, and Google Scholar databases covering the period 2016–2025 using relevant keywords related to UC-MSC and RA. Bibliometric analysis was performed using VOSviewer to map publication trends, scientific collaborations, and research topic clusters, while the literature review was used to evaluate the underlying mechanisms and therapeutic effectiveness. The results indicate a significant increase in UC-MSC research in recent years, with a primary focus on immunomodulatory mechanisms and clinical applications. Biologically, UC-MSCs have been shown to suppress synovial hyperplasia, inhibit pro-inflammatory cytokine production, and increase regulatory T cell (Treg/FOXP3) populations, thereby promoting immune tolerance and tissue repair. Preclinical and clinical studies have reported reductions in disease activity scores and improvements in joint function. However, the limited number of large-scale clinical trials and insufficient exploration of specific molecular mechanisms remain major challenges. Therefore, further studies are required to optimize the clinical application of UC-MSCs as a regenerative and immunomodulatory therapy for RA.
Downloads
References
[1] W. Science, “Analysis Of Modern Preventive Measures In Dental Implantation In Patients With Rheumatoid Arthritis,” London Int. Mon. Conf. Multidiscip. Res. Innov., pp. 308–310, 2026.
[2] R. Irshad, H. Yaseen, T. Bibi, T. Saleem, and Z. Sharif, “Correlation of C-reactive protein , antinuclear antibodies and anti-cyclic citrullinated peptide with rheumatoid arthritis : A mini review,” Electron. J. Med. Res., pp. 1–5, 2026.
[3] M. M. Hanlon and E. M. Gravallese, “Synovial Tissue Macrophage Heterogeneity in Rheumatoid Arthritis,” Eur. J. Immunol. Rev., 2026, doi: 10.1002/eji.70124.
[4] S. Grabar, M. Leja, C. J. Alberts, P. Bloem, and S. De Sanjos, “European Code Against Cancer , 5th edition – cancer- causing infections and related interventions,” Mol. Oncol., vol. 20, pp. 96–116, 2026, doi: 10.1002/1878-0261.70172.
[5] A. N.- Acien. Zhou, “JAHA at Scientific Sessions 2024 : Climate Change – Related Cardiovascular Health Effects in the Global South,” J. Am. Hear. Assoc. Downloaded, pp. 1–8, 2026, doi: 10.1161/JAHA.125.044079.
[6] E. Grywalska., “Elevated expression of immune checkpoints and pro-inflammatory cytokines as potential biomarkers in pediatric Vulvar Lichen Sclerosus IN AR IN,” Sci. Rep., 2026.
[7] K. Torfs, T. Devos, and P. Proost, “Neutrophils as critical orchestrators of chronic in fl ammation,” Rev. Artic., no. July 2025, 2026, doi: 10.1038/s41423-025-01380-w.
[8] V. Tasouli-drakou, D. Rodriguez, V. Krutikova, and A. Mohammadi, “The Impact of Disease-Modifying Antirheumatic Drugs on In-Hospital Outcomes of Patients With COVID-19 : A Retrospective Cohort Study and Literature Review,” Cureus, vol. 18, no. 1, pp. 1–12, 2026, doi: 10.7759/cureus.102637.
[9] M. Soltani, S. Falahi, M. Abbaszadeh, M. J. M. Sullman, H. Fouladseresht, and N. Eskandari, “Neutrophil Plasticity and NETosis in Tumour Microenvironment : Tumour Evolution and Therapy Resistance,” J. Immunol. Res., vol. 2026, 2026, doi: 10.1155/jimr/5568021.
[10] T. Xu., “Exploring the role of unconventional T cells in rheumatoid arthritis,” Front. Imunol., no. August, pp. 1–12, 2025, doi: 10.3389/fimmu.2025.1656994.
[11] H. F. Hetta, “Clinical Progress in Mesenchymal Stem Cell Therapy : A Focus on Rheumatic Diseases,” Immunity, Inflamm. Dis. Rev., 2025, doi: 10.1002/iid3.70189.
[12] W. Huang, “Functionalized mesenchymal stem cells for enhanced bone regeneration : advances and challenges,” Stem Cell Res. Ther., 2025.
[13] H. Mao, X. Zhao, and S. Sun, “NF- κ B in in fl ammation and cancer,” Cell. Mol. Immunol., no. March, 2025, doi: 10.1038/s41423-025-01310-w.
[14] L. Yin, C. Sun, G. Chen, and Z. Xiang, “Modular mastery of in fl ammation : umbilical cord mesenchymal stem cells as a therapeutic frontier,” Front. Imuunology, no. December, pp. 1–19, 2025, doi: 10.3389/fimmu.2025.1721947.
[15] L. Wang, Y. Liang, C. Zhao, P. Ma, S. Zeng, and D. Ju, “Regulatory T cells in homeostasis and disease : molecular mechanisms and therapeutic potential,” Signal Transduct. Target. Ther., no. August 2024, pp. 1–31, 2025.
[16] P. Shi, Y. Yu, H. Xie, X. Yin, and X. Chen, “Recent advances in regulatory immune cells : exploring the world beyond Tregs,” Front. Imunol., no. May, pp. 6–9, 2025, doi: 10.3389/fimmu.2025.1530301.
[17] M. Kakh, “Induction of Regulatory T Cells After Virus Infection and Vaccination,” Immunology, vol. 3, pp. 1–16, 2025, doi: 10.1111/imm.13927.
[18] W. Liming, “Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients : A Prospective Phase I / II Study,” Drug Des. Devel. Ther., pp. 4331–4340, 2019.
[19] X. He, “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] D. Ma, “Immunomodulatory effect of human umbilical cord mesenchymal stem cells on T lymphocytes in rheumatoid arthritis,” Int. Immunopharmacol., vol. 74, p. 105687, 2019, doi: https://doi.org/10.1016/j.intimp.2019.105687.
[21] L. Liu, “Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arthritis,” EBioMedicine, vol. 47, pp. 563–577, 2019, doi: https://doi.org/10.1016/j.ebiom.2019.08.073.
[22] K. Xu., “Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorate collagen-induced arthritis via immunomodulatory T lymphocytes,” Mol. Immunol., vol. 135, pp. 36–44, 2021, doi: https://doi.org/10.1016/j.molimm.2021.04.001.
[23] R. Kumar, “Bibliometric Analysis : Comprehensive Insights into Tools , Techniques , Applications , and Solutions for Research Excellence,” Spectr. Eng. Manag. Sci., vol. 3, no. 1, pp. 45–62, 2025.
[24] R. K. Anwar, A. Z. Abidin, Y. Winoto, and U. Padjadjaran, “A Bibliometric Study on the Development of Radio Broadcasting Literature,” Jurnalisme, vol. 08, no. 02, 2025.
[25] C. Zhao, “Umbilical Cord-Derived Mesenchymal Stem Cells Inhibit Cadherin-11 Expression by Fibroblast-Like Synoviocytes in Rheumatoid Arthritis,” vol. 2015, 2015, doi: 10.1155/2015/137695.
[26] E. Gonzalo-gil, “Human embryonic stem cell-derived mesenchymal stromal cells ameliorate collagen-induced arthritis by inducing host- derived indoleamine 2 , 3 dioxygenase,” Arthritis Res. Ther., pp. 1–9, 2016, doi: 10.1186/s13075-016-0979-0.
[27] Q. Chen, “Mesenchymal stem cells regulate the Th17 / Treg cell balance partly through hepatocyte growth factor in vitro,” Stem Cell Res. Ther., pp. 1–11, 2020.
[28] P. Luz-crawford, “Mesenchymal stem cells generate a CD4 + CD25 + Foxp3 + regulatory T cell population during the differentiation process of Th1 and Th17 cells,” Stem Cell Res. Ther., 2018.
[29] N. Petryk and O. Shevchenko, “Mesenchymal Stem Cells Anti-Inflammatory Activity in Rats : Proinflammatory Cytokines Mesenchymal Stem Cells Anti-In fl ammatory Activity in Rats : Proin fl ammatory Cytokines,” J. Inflamm. Res., vol. 7031, 2020, doi: 10.2147/JIR.S256932.
[30] Q. Meng and B. Qiu, “Exosomal MicroRNA-320a Derived From Mesenchymal Stem Cells Regulates Rheumatoid Arthritis Fibroblast-Like Synoviocyte Activation by Suppressing CXCL9 Expression,” Orig. Res., vol. 11, no. May, pp. 1–14, 2020, doi: 10.3389/fphys.2020.00441.
[31] Y. Liu, “Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis,” Arthritis Res. Ther., pp. 1–13, 2020.
[32] C. Yang, M. Wu, M. You, Y. Chen, M. Luo, and Q. Chen, “The therapeutic applications of mesenchymal stromal cells from human perinatal tissues in autoimmune diseases,” Stem Cell Res. Ther., pp. 1–15, 2021.
[33] Y. Zhao., “UC-MSC Modulate Macrophage Polarization in Autoimmune Arthritis,” Stem Cell Res. Ther., pp. 1–23, 2021, doi: 10.1186/s13287-021-02602-4.
[34] M. Lopez-santalla, J. A. Bueren, and M. I. Garin, “EBioMedicine Mesenchymal stem / stromal cell-based therapy for the treatment of rheumatoid arthritis : An update on preclinical studies,” EBioMedicine, vol. 69, p. 103427, 2021, doi: 10.1016/j.ebiom.2021.103427.
[35] X. Lv, “Umbilical Cord Mesenchymal Stem Cell Therapy for Regenerative Treatment of Rheumatoid Arthritis : Opportunities and Challenges,” Drug Des. Devel. Ther., pp. 3927–3936, 2021.
[36] R. Morochoviˇ, P. Gašparov, and J. Živˇ, “Interaction between Mesenchymal Stem Cells and the Immune System in Rheumatoid Arthritis,” Pharm. Rev., 2022.
[37] J. Gu, “Human umbilical cord mesenchymal stem cells improve the immune ‑ associated inflammatory and prothrombotic state in collagen type ‑ Ⅱ ‑ induced arthritic rats,” Mol. Med. Rep., pp. 7463–7470, 2025, doi: 10.3892/mmr.2015.4394.
[38] E. W. Choi, I. R. Lim, J. H. Park, J. Song, B. Choi, and S. Kim, “Exosomes derived from mesenchymal stem cells primed with disease ‑ condition ‑ serum improved therapeutic efficacy in a mouse rheumatoid arthritis model via enhanced TGF ‑ β1 production,” Stem Cell Res. Ther., pp. 1–17, 2023, doi: 10.1186/s13287-023-03523-0.
[39] Z. Deng., “Human umbilical cord mesenchymal stem cells on treating osteoarthritis in a rabbit model : Injection strategies,” Heliyon, vol. 10, no. September, 2024.
[40] Bakinowska, “The Role of Mesenchymal Stromal Cells in the Treatment of Rheumatoid Arthritis,” Cells, pp. 1–17, 2024.
[41] Z. Chen, “The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells,” Chinese J. Traumatol., vol. 27, no. 1, pp. 1–10, 2024, doi: https://doi.org/10.1016/j.cjtee.2023.11.003.
[42] X. Wang, “From mitochondria to immune networks : new mesenchymal stem cell strategies to treat periodontitis,” Stem Cell Res. Ther., 2025.
[43] S. Wang, K. Zhang, L. Wang, and Y. Guo, “Stem Cell-Derived Exosomes with High Expression of PD-L1 as Nanotherapeutics in Rheumatoid Arthritis Model Mice,” Int. J. Nanomedicine Open, no. July, pp. 8935–8949, 2025.
[44] Y. Sun, “Comparable therapeutic potential of umbilical cord mesenchymal stem cells in collagen-induced arthritis to TNF inhibitor or anti-CD20 treatment,” Rheumatol. Immunol., pp. 288–295, 2025.
[45] L. Zeng, “Efficacy and safety of mesenchymal stromal cell transplantation in the treatmenat of autoimmune and rheumatic immune diseases : a systematic review and meta ‑ analysis of randomized controlled trials,” Stem Cell Res. Ther., 2025, doi: 10.1186/s13287-025-04184-x.
[46] Y. Gao, N. Zhao, and C. Hu, “Harnessing mesenchymal stem / stromal cells-based therapies for rheumatoid arthritis : mechanisms , clinical applications , and microenvironmental interactions,” Stem Cell Res. Ther., 2025.
[47] Y. Chen and Y. E. Liu, “Mesenchymal stromal cell therapy for rheumatoid arthritis : Long ‐ term e ffi cacy , safety , and mechanistic insights,” Rheumatol. Autoimmun., no. July, pp. 1–13, 2025, doi: 10.1002/rai2.70032.
[48] F. L. Margareta, Y. Nugraha, B. Nurcita, and C. Fauziah, “Potential Of Umbilical Cord Mesenchymal Stem Cell ( Uc-Msc ) In Therapy Of Rheumatoid Arthritis ( RA ),” Rehumatology, vol. X, pp. 44–52, 2022.
[49] W. Jia, “Development of mesenchymal stem cells : therapeutic effect and prospect for rheumatoid arthritis,” Stem Cell Res. Ther., 2026.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Bastian Bastian, Radiyati Umi Partan, Krisna Murti, Ayeshah Augusta Rosdah
This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.
Copyright in each article is the property of the Author.
