Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

Abstract

Mesenchymal stem cell (MSC) therapy represents a promising approach for the treatment of osteoarthritis (OA). MSCs can be readily isolated from multiple sources and expanded ex vivo for possible clinical application. They possess a unique immunological profile and regulatory machinery that underline their therapeutic effects. They also have the capacity to sense the changes within the tissue environment to display the adequate response. Indeed, there is a close interaction between MSCs and the host cells. Accordingly, MSCs demonstrate encouraging results for a variety of diseases including OA. However, their effectiveness needs to be improved. In this review, we selected to discuss the importance of the immunological features of MSCs, including the type of transplantation and the immune and blood compatibility. It is important to consider MSC immune evasive rather than immune privileged. We also highlighted some of the actions/mechanisms that are displayed during tissue healing including the response of MSCs to injury signals, their interaction with the immune system, and the impact of their lifespan. Finally, we briefly summarized the results of clinical studies reporting on the application of MSCs for the treatment of OA. The research field of MSCs is inspiring and innovative but requires more knowledge about the immunobiological properties of these cells. A better understanding of these features will be key for developing a safe and efficient medicinal product for clinical use in OA.

Immunomodulatory Actions of Mesenchymal Stromal Cells (MSCs) in Osteoarthritis of the Knee

“…Despite the disappearance of administered MSCs from the site, they elaborate the cytokines and chemokines which work by paracrine signaling and induce the quiescent and resident MSCs to enhance the significant therapeutic effects [23]. Hence the dead MSCs exert a non-specific immunomodulatory environment in the osteoarthritis of the knee through apoptosis, complement-mediated cell death, autophagy, and senescence [39]. The paracrine and the contact immunomodulatory effects of MSCs on the immune cells are given in Figures 1 and 2 Apoptotic MSCs interact with immune cells directly by apoptosis and indirectly by phagocytosis.…”

Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging

“…MSCs from umbilical cord blood [ 74 ] and amnion [ 75 ], showed increase of cytokines and chemokines associated with their TLR5 and TLR6 expression. This increase may promote the migration of MSCs from adipose tissue to target tissues [ 76 ] as well as favor a tolerogenic environment suitable for tissue regeneration [ 77 ]. Finally, as differential utilization of TIR domain-containing adaptors may provide specificity of individual TLR-mediated signaling pathways, we aimed to have a view on the proteins and functional interactions that may occur.…”

Preservation of microvascular integrity and immunomodulatory property of prevascularized human mesenchymal stem cell sheets

“…Even though hMSCs are not completely immunosuppressive, such as the aggregated delivery initiates immune responses (Veiseh et al., 2015), they can modulate innate immune responses (Najar, Martel‐Pelletier, Pelletier, & Fahmi, 2020). One of the remarkable benefits of hMSCs is that their paracrine factors can suppress B‐ and T‐cell proliferation and modulate immune cell activity toward tissue regeneration (Bernardo & Fibbe, 2013), which could reduce the risk of graft rejection and promote tissue integration.…”