A comprehensive review on the role of mesenchymal stromal/stem cells in the management of rheumatoid arthritis

ABSTRACT

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease with systemic manifestations. Although the success of immune modulatory drug therapy is considerable, about 40% of patients do not respond to treatment. Mesenchymal stromal/stem cells (MSCs) have been demonstrated to have therapeutic potential for inflammatory diseases.

Areas covered

This review provides an update on RA disease and on pre-clinical and clinical studies using MSCs from bone marrow, umbilical cord, adipose tissue, and dental pulp, to regulate the immune response. Moreover, the clinical use, safety, limitations, and future perspective of MSCs in RA are discussed. Using the PubMed database and ClincalTrials.gov, peer-reviewed full-text papers, abstracts and clinical trials were identified from 1985 through to April 2023.

Expert opinion

MSCs demonstrated a satisfactory safety profile and potential for clinical efficacy. However, it is mandatory to deepen the investigations on how MSCs affect the proinflammatory deregulated RA patients’ cells. MSCs are potentially good candidates for severe RA patients not responding to conventional therapies but a long-term follow-up after stem cells treatment and standardized protocols are needed. Future research should focus on well-designed multicenter randomized clinical trials with adequate sample sizes and properly selected patients satisfying RA criteria for a valid efficacy evaluation.

KEYWORDS:

• Immune-modulation
• inflammation
• mesenchymal stem cells
• rheumatoid arthritis
• safety
• stem cells

Article highlights

• Owing to incomplete responsiveness of RA patients to current therapies, stem cells are becoming an alternative approach to improve the immune response to treatment.

• UC-MSCs, AD-MSCs and G-MSCs in pre-clinical studies showed the best efficacy compared to all the other sources of MSCs but a dose-response relationship of MSC therapy is needed before undertaking clinical trials.

• Intra-articularly injected MSCs, rather than systemic, appeared to be safe in the short-term period.

• Many clinical trials have not reached the required endpoints. Future research should focus on well-designed multicenter randomized clinical trials and longer follow-up periods for a valid efficacy evaluation.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by Fondo di Ateneo per la Ricerca (FAR) 2019 interdisciplinare AGAPI prot no 0166819/2019 of the University of Modena and Reggio Emilia; Fondo di Ateneo per la Ricerca (FAR) 2020 of the University of Modena and Reggio Emilia (prot. no. 0172869/2020); Progetto Ricerca Finalizzata 2019 Ministero Salute, project code RF-2019-12370609.