Interaction between Mesenchymal Stem Cells and the Immune System in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that causes damage to joints. This review focuses on the possibility of influencing the disease through immunomodulation by mesenchymal stem cells (MSCs). There is an occurrence of rheumatoid factor and RA-specific autoantibodies to citrullinated proteins in most patients. Citrulline proteins have been identified in the joints of RA patients, and are considered to be the most suitable candidates for the stimulation of anti-citrulline protein antibodies production. Fibroblast-like proliferating active synoviocytes actively promote inflammation and destruction in the RA joint, in association with pro-inflammatory cells. The inflammatory process may be suppressed by MSCs, which are a population of adherent cells with the following characteristic phenotype: CD105+, CD73+, CD90+, CD45−, CD34− and HLA DR−. Following the stimulation process, MSCs are capable of immunomodulatory action through the release of bioactive molecules, as well as direct contact with the cells of the immune system. Furthermore, MSCs show the ability to suppress natural killer cell activation and dendritic cells maturation, inhibit T cell proliferation and function, and induce T regulatory cell formation. MSCs produce factors that suppress inflammatory processes, such as PGE2, TGF-β, HLA-G5, IDO, and IL-10. These properties suggest that MSCs may affect and suppress the excessive inflammation that occurs in RA. The effect of MSCs on rheumatoid arthritis has been proven to be a suitable alternative treatment thanks to successful experiments and clinical studies.

Mesenchymal Stem Cell Priming: Potential Benefits of Administration of Molecular Hydrogen

“…The clinical implications of MSC priming with molecular hydrogen for anti-inflammatory purposes may be profound. Consider autoimmune diseases like rheumatoid arthritis, where the immune system mistakenly attacks the body’s own tissues, leading to chronic inflammation and joint damage [ 49 ]. Primed MSCs have the potential to exert more robust control over the inflammatory processes at play, offering relief to patients and potentially slowing the progression of the disease.…”

“…Furthermore, this avenue of research highlights the versatility and adaptability of MSC-based therapies. By enhancing the inherent anti-inflammatory properties of these cells, priming with molecular hydrogen represents a promising strategy for addressing a wide array of diseases characterized by immune dysregulation and excessive inflammation [ 49 ]. As our understanding deepens and the clinical evidence accumulates, the convergence of MSCs and molecular hydrogen priming could become a cornerstone in the management of inflammatory disorders, ushering in a new era of precision medicine and improved patient outcomes.…”

Human Chondrocytes, Metabolism of Articular Cartilage, and Strategies for Application to Tissue Engineering

“…This can further initiate the process of apoptosis in the affected cells. Specifically, TNF-α inhibits chondrogenic differentiation, which is linked to p38 mitogen-activating protein kinase (MAPK) [24,101]. In addition to TNF-α, inflammatory cells also secrete interferon-γ (IFN-γ), which suppresses proliferation, and negatively affect the viability of chondrocytes.…”

Apoptotic Vesicles of MSCs: The Natural Therapeutic Agents and Bio‐Vehicles for Targeting Drug Delivery

“…Other immunomodulatory substances, such as interleukin (IL)−4, IL-10, indoleamine 2,3-dioxygenase, and IL-6 are involved in regulating host immune responses and strongly influencing the innate and adaptive immune cells. [6][7][8] MSC-derived exosomes and microvesicles also exert therapeutic effects in various diseases by horizontally transferring proteins, mRNAs, and regulatory microRNA. [9] Additionally, the expression of multiple receptors of the chemokines, such as C-X-C chemokine receptor type 4 (CXCR4) endows MSCs with targeting ability to disease tissues.…”