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Therapeutic Potential of Mesenchymal Stromal Stem Cells in Rheumatoid Arthritis: a Systematic Review of In Vivo Studies

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Abstract

Standard treatment options for rheumatoid arthritis (RA) often fail to deliver a long-term therapeutic outcome and in many cases cause intractable adverse events leading to treatment discontinuation or readjustment. Treatment with mesenchymal stem cells (MSCs) has been recently studied in RA due to its immunomodulatory and anti-inflammatory capacities. Thus, this study aims at systematically search and review the literature for randomized or non-randomized clinical trials comparing interventions of MSCs with placebo in RA patients. Electronic searches were conducted on PubMed, SCOPUS, Cochrane-CENTRAL, registries of clinical trials and grey literature. Selected studies were estimated for risk of bias with the Cochrane RoB tool 2 or the ROBINS-I tool. Four trials met the eligibility criteria and entered the review process. Identified MSCs treatments varied from allogeneic to autologous or umbilical cord-derived cells. Enrolled patients had an active RA and had poor responses to previous standard medications. In general, the safety evaluation revealed that treatment with MSCs was safe and well tolerated. Regarding the efficacy measurements, modest improvements were found in RA symptoms and RA-related indices. Significant decreases were found in inflammatory molecules such as C-reactive protein, tumor necrosis factor alpha and interleukin 6. However, clinical response criteria related to RA were achieved by a low-to-moderate percentage of patients. In conclusion, treatment of RA with MSCs appears to have a short-term therapeutic effect. Better-designed randomized trials with sufficient follow-up periods are needed so that the long-term safety and efficacy interventions with MSCs would be elucidated.

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Authors and Affiliations

Authors

Contributions

Alexia K and Aristeidis K: conceive the study. Alexia K: systematic search, screening for eligibility, data extraction, bias and quality assessment, and drafting of the manuscript. DA: systematic search, screening for eligibility and drafting the manuscript. AB: data extraction and drafting the manuscript. KG: bias and quality assessment, and drafting the manuscript. Aristeidis K: systematic search, screening for eligibility, data extraction, bias and quality assessment, and drafting the manuscript. All authors: contribution in the design of the work, interpretation of data, critical revision for important intellectual content, approval of the final version of the manuscript to be published, and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Alexia Karamini or Aristeidis Kritis.

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Karamini, A., Bakopoulou, A., Andreadis, D. et al. Therapeutic Potential of Mesenchymal Stromal Stem Cells in Rheumatoid Arthritis: a Systematic Review of In Vivo Studies. Stem Cell Rev and Rep 16, 276–287 (2020). https://doi.org/10.1007/s12015-020-09954-z

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