# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 4 MSC-Based Therapy for OA
### General Characteristics
To be effective, a therapy based on MSCs must fulfil at least these three essential requirements: an acceptable cell count, the survival of the joint, and the capacity for chondrocyte development. MSCs are distinguished by the following characteristics:  
_Plasticity:_ because of their ability to self-renew, maintain stemness, and maintain cell potency, MSCs may aid tissue healing. They can differentiate into a range of mesodermal tissues and migrate to sites of injury where they demonstrate topic effects [133]. _Topic effects:_ MSCs govern the synthesis of proliferative, angiogenesis-promoting, and regenerative chemicals [133; 134]: granulocyte-colony stimulating factor (G-CSF), stem cell factor (SCF), macrophage colony-stimulating factor (M-CSF), IL-6, and decreased serum TNF-\(\alpha\) levels. MSCs have immunosuppressive and immunomodulatory effects on lymphocytes [135], B cells [136], dendritic cells (DC) [137], and natural killer cells (NKC) [135; 136; 137; 138]. MSCs  
Figure 1: MSCs may result from a variety of tissues (bone marrow, adipose tissue, umbilical cord, synovium, dental pulp, dermis) and are able to transform into structures’ cells involved in OA development and management. respond to inflammation by migrating into wounded tissue, where they regulate immune and inflammatory responses and promote tissue healing. It has been demonstrated that MSCs can influence innate and adaptive immune responses. MSCs govern the production of cytokines by DC and Th1/Th2 cells [139], restrict the maturation and activation of cells antigen presentation (APCs), and regulate the development of CD4+CD25+ regulatory cells [140]. _Therapeutic effects_: owing to their ability to differentiate into numerous cell types, including myocytes, tenocytes, and ligament cells, MSCs appear to be a viable therapy option for knee OA [111; 112]. MSCs were initially used to treat knee osteoarthritis in a carbine mensicectomy model 2003. The therapy group demonstrated significant medial meniscus regeneration. Degeneration of articular cartilage, osteophytic remodeling, and subchondral sclerosis were also reduced. Since the administered MSCs were found in soft tissue rather than articular cartilage, it is unlikely that MSCs contribute directly to cartilage regeneration [141]. The tropical characteristics of MSCs are more likely to promote cartilage repair than chondrogenic differentiation. [PERSON] et al. [142] demonstrated that MSCs encourage chondrocyte proliferation and matrix deposition by secretion water-soluble compounds. Recently, [PERSON] et al. [143] reported positive outcomes in two knee OA patients treated with MSCs, HA, dexamethasone, and PRP. After three months, subjective (pain and function) and objective (MRI evidence of cartilage thickness) outcomes (cartilage thickness) improved. However, it is difficult to determine which therapy intervention contributed more to the results because of the multimodal treatment approach. In a study conducted by [PERSON] et al., a five-year follow-up was conducted whereby three patients were administered exclusive mesenchymal stem cell (MSC) treatment. Significant improvements were seen in discomfort and function, as shown by several measures such as walking time, number of ascended steps, gelling pain, patella crepitus, flexion contracture, and the visual analog scale for pain. Typically, therapy benefits decline over time, but these patients remained considerably better than at baseline after five years. Furthermore, there was an observed improvement in the Patient Global Assessment (PGA) from the first measurement to the five-year time point. The knee that exhibited superior condition at the initial stage but did not get mesenchymal stem cell (MSC) treatment saw ongoing deterioration over five years, ultimately becoming the inferior knee [144]. There needs to be more clinical evidence derived from long-term, randomized, double-masked, controlled, multicenter studies with thorough follow-up.