Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review

Abstract

With the insufficient satisfaction rates and high cost of operative treatment for osteoarthritis (OA), alternatives have been sought. Furthermore, the inability of current medications to arrest disease progression has led to rapidly growing clinical research relating to mesenchymal stem cells (MSCs). The availability and function of MSCs vary according to tissue source. The three primary sources include the placenta, bone marrow, and adipose tissue, all of which offer excellent safety profiles. The primary mechanisms of action are trophic and immunomodulatory effects, which prevent the further degradation of joints. However, the function and degree to which benefits are observed vary significantly based on the exosomes secreted by MSCs. Paracrine and autocrine mechanisms prevent cell apoptosis and tissue fibrosis, initiate angiogenesis, and stimulate mitosis via growth factors. MSCs have even been shown to exhibit antimicrobial effects. Clinical results incorporating clinical scores and objective radiological imaging have been promising, but a lack of standardization in isolating MSCs prevents their incorporation in current guidelines.

Keywords: adipose tissue; bone marrow; mesenchymal stem cells; osteoarthritis; placenta; stromal vascular fraction.

Figure 1

A summary of mesenchymal stem cell (MSC) effects. IDO—Indoleamine 2,3-dioxygenase; ADO—adenosine; PD-L1—programmed cell death ligand 1; PD-L2—programmed cell death ligand 2; TGF-β—transforming growth factor β; HGF—hepatocyte growth factor; CCL2—monocyte chemoattractant protein 1 (MCP-1); PGE2—prostaglandin E2; HO-1—heme oxygenase-1; HLA-G—human leukocyte antigen-G; IL-10—interleukin 10; TSG-6—tumor necrosis factor-stimulated gene 6; IL-1Ra—interleukin 1 receptor antagonist; DC—dendritic cells; IFN-γ—interferon-γ; HBD—human b-defensins; lcn2—lipocain family; FGF—fibroblast growth factor; IGF—insulin growth factor; VEGF—vascular endothelial growth factor; STC1—stanniocalcin-1; TIMP2—tissue inhibitor of metalloproteinases 2; ADAMTS—a disintegrin and metalloproteinase with thrombospondin motifs; SDF—stromal cell-derived factor; SFRP2—secreted fizzled related protein. Created with BioRender.com.