Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects the lining of the synovial joints leading to stiffness, pain, inflammation, loss of mobility, and erosion of joints. Its pathogenesis is related to aberrant immune responses against the synovium. Dysfunction of innate and adaptive immunity, including dysregulated cytokine networks and immune complex-mediated complement activation, are involved in the progression of RA. At present, drug treatments, including corticosteroids, antirheumatic drugs, and biological agents, are used in order to modulate the altered immune responses. Chronic use of these drugs may cause adverse effects to a significant number of RA patients. Additionally, some RA patients are resistant to these therapies. In recent years, mesenchymal stem/stromal cell (MSCs)-based therapies have been largely proposed as a novel and promising stem cell therapeutic approach in the treatment of RA. MSCs are multipotent progenitor cells that have immunomodulatory properties and can be obtained and expanded easily. Today, nearly one hundred studies in preclinical models of RA have shown promising trends for clinical application. Proof-of-concept clinical studies have demonstrated satisfactory safety profile of MSC therapy in RA patients. The present review discusses MSC-based therapy approaches with a focus on published clinical data, as well as on clinical trials, for treatment of RA that are currently underway.

Keywords: cell therapy protocols; clinical trials; mesenchymal stem/stromal cells; rheumatoid arthritis.

Figure 1

Characteristics of the completed rheumatoid arthritis (RA) clinical trials. (A) RA disease status of patients; (B) major histocompatibility complex (MHC) context (C) MSC tissue source. Umbilical cord (UC-MSCs), adipose tissue (AD-MSCs), and bone marrow (BM-MSCs); (D) number of doses and (E) MSC dose expressed as number of cells/kg of body weight (1–10 × 10⁶ or >10–50 × 10⁶). Data are represented as percentage of the total number of studies.

Figure 2

Characteristics of the open RA clinical trials. (A) RA disease status of patients; (B) MHC context (C) MSC tissue source. Umbilical cord (UC-MSCs), adipose tissue (AD-MSCs) and bone marrow (BM-MSCs); (D) number of MSCs infusions and (E) MSC dose expressed as number of cells/kg of body weight (1–10 × 10⁶). Data are represented as percentage of the total number of studies.

Figure 3

Cumulative number and phase of registered clinical trials with MSC-based therapy in RA patients according to the year of registration in ‘www.ClinicalTrials.gov’ and ‘Pubmed’ databases.