Mesenchymal Stem/Stromal Cells in Osteoarthritis: Navigating a Long and Challenging Path

Mesenchymal stem/stromal cell (MSC)-based therapies have emerged as a promising approach in the treatment of osteoarthritis (OA), offering new hope for millions of patients worldwide. These innovative therapeutic strategies aim to address the underlying causes of OA by exploiting the regenerative and immunomodulatory properties of MSCs. Recent advancements in this field have demonstrated the multifaceted potential of MSCs in mitigating OA symptoms and slowing disease progression through several key mechanisms: (i) Pain reduction and functional improvement: clinical studies have thus shown that intra-articular (IA) injection of MSCs can lead to significant pain alleviation and improved joint function in OA patients. (ii) Cartilage preservation and regeneration: MSCs exhibit chondroprotective properties, contributing to the maintenance of existing cartilage and potentially stimulating the repair of damaged tissue. (iii) Anti-inflammatory and immunomodulatory effects: MSC have the ability to modulate the inflammatory environment within the joint by secreting bioactive factors that can reduce pro-inflammatory cytokine levels, promote anti-inflammatory mediators and modulate immune cell activity. While the exact mechanisms of action are not yet fully understood, it is suggested that the therapeutic effects of MSCs are likely to be mediated through paracrine signaling rather than long-term engraftment in joint tissues. The field of MSC-based therapies for OA is rapidly evolving, with current investigations focused on optimizing treatment protocols (cell dosage and frequency of injection..); identifying the most effective cell sources (bone marrow, adipose tissue..); enhancing cell preparation (homogeneity) and delivery methods (encapsulating biomaterials); and exploring combination therapies with other regenerative approaches. This presentation will provide an overview of the latest findings in MSC-based treatments for OA with an objective discussion of their clinical implications. By examining the potential benefits and current limitations, we will contribute to better understand the positioning of MSC therapies in OA management from a patient-oriented perspective.