State of the Art: The Immunomodulatory Role of MSCs for Osteoarthritis

Abstract

Osteoarthritis (OA) has generally been introduced as a degenerative disease; however, it has recently been understood as a low-grade chronic inflammatory process that could promote symptoms and accelerate the progression of OA. Current treatment strategies, including corticosteroid injections, have no impact on the OA disease progression. Mesenchymal stem cells (MSCs) based therapy seem to be in the spotlight as a disease-modifying treatment because this strategy provides enlarged anti-inflammatory and chondroprotective effects. Currently, bone marrow, adipose derived, synovium-derived, and Wharton’s jelly-derived MSCs are the most widely used types of MSCs in the cartilage engineering. MSCs exert immunomodulatory, immunosuppressive, antiapoptotic, and chondrogenic effects mainly by paracrine effect. Because MSCs disappear from the tissue quickly after administration, recently, MSCs-derived exosomes received the focus for the next-generation treatment strategy for OA. MSCs-derived exosomes contain a variety of miRNAs. Exosomal miRNAs have a critical role in cartilage regeneration by immunomodulatory function such as promoting chondrocyte proliferation, matrix secretion, and subsiding inflammation. In the future, a personalized exosome can be packaged with ideal miRNA and proteins for chondrogenesis by enriching techniques. In addition, the target specific exosomes could be a gamechanger for OA. However, we should consider the off-target side effects due to multiple gene targets of miRNA.

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

“…Furthermore, it is clear that the properties of MSCs differ depending on the organ from which they are collected. Adipose-derived MSCs, as well as bone-marrow-derived MSCs, have received a great deal of attention because they can be collected more easily and abundantly throughout the body, are less invasive, and have excellent organ repair and immunomodulatory abilities, compared with those of bone-marrow-derived MSCs [ 170 , 171 ]. Bone-marrow-derived MSCs comprise only approximately 0.01% of the cells in the bone marrow, whereas the number of adipose-derived MSCs in adipose tissue is 500 times that of MSCs in the bone marrow.…”

Osteoarthritis as an Umbrella Term for Different Subsets of Humans Undergoing Joint Degeneration: The Need to Address the Differences to Develop Effective Conservative Treatments and Prevention Strategies

“…Single-cell injections have not proven to be very effective in repairing damaged cartilage, but they have been effective in clinical trials to affect pain and disability [ 99 , 100 ]. However, effectiveness may be negatively influenced by the intra-articular environment, particularly the presence of inflammation [ 4 , 101 ], in spite of their possible immunomodulatory role [ 102 , 103 ]. Some pilot studies with tissue-engineered constructs with autologous synovium-derived mesenchymal stem/stromal cells have indicated the good potential to restore cartilage in cartilage defects prior to the development of overt knee OA [ 104 , 105 ].…”

Osteoarthritis: Advances and Emerging Treatments

“…42 The exosomes themselves are much smaller than MSCs, which is advantageous in terms of delivery; however, it is not yet fully understood what the off-target effects of microRNA will touchREVIEWS in RMD be, and this will require considerable study before the hope of a licensed DMOAD can be realized. 43 Finally, matrix metalloproteinase-13 is expressed by chondrocytes and synovial cells in human OA and is thought to play a critical role in cartilage destruction. A recent publication has reported the development of a new allosteric metalloproteinase-13 inhibitor, AQU-019, which has been developed as a new DMOAD.…”