# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 4 MSC-Based Therapy for OA
### General Characteristics
Furthermore, the existing body of research suggests a wide range of doses and ways to administer MSCs, rendering it impractical to compare clinical results [145]. Moreover, the optimal setting for cartilage tissue regeneration remains unknown. Additional research is necessary to determine the appropriate MSCs dose. Standardizing techniques will facilitate MSC research in this industry. _Safety/contraindications_, _side-effects_: even if the use of stem cells in therapeutic trials has shown some promise, caution should still be maintained [146]. In cartilage abnormalities, there are still a few metabolic pathways that can potentially affect the fate of transplanted MSCs. To make matters even more complicated, no one is aware of a way to stop MSCs chondrogenesis from occurring in the first place. Figure 2 explains the roles of MSCs in cartilage regeneration [111; 147; 148; 149]. The development of mesenchymal stem cells (MSCs) is regulated by various stimuli, including transcription factors, cytokines, growth factors, and components of the extracellular matrix [150]. The effectiveness of differentiation is also contingent upon the age of the patient, as shown by the observation that isolated cells from younger patients have a superior ability to undergo differentiation in a culture setting [151]. Various markers distinguish between adipogenic, chondrogenic, and osteogenic lineages. Biomarkers for adipogenic differentiation include adiponectin, CCAAT/enhancer binding protein (C/EBP), Fatty Acid-Binding Protein 4 (FABP4), and leptin; PPAR, aggreccan collagen type II (Col II) and SRY-Box Transcription Factor 9 (Sox9) are biomarkers for chondrogenic differentiation; and alkaline phosphatase, bone sialoprotein, osteoclast, and Runk2 are biomarkers for osteogenic differentiation [152,153]. Although the criteria for classifying human MSCs are fluid and subject to change, most studies concur on the three distinguishing features of human MSCs defined by the International Society for Cellular Therapy (IST) [128,154]. Figure 3 highlights these features. 1. Plastic adherence is the first general characteristic of MSCs; it permits the maintenance of clonally growing cells in plastic culture plates for numerous passages without removing the subpopulation of cells with hematopoietic activities [154,155]. Figure 3: International Society for Cellular Therapy (IST) 2006 criteria for MSCs. Figure 2: Recognized mechanisms by which MSCs can influence cartilage repair in OA. The ICST has endorsed CD105 (endoglin), CD73 (ecto-5' -nuclease), and CD90 (Thy-1) as positive and negative surface markers for MSCs. In contrast, MSCs lack the expression of hematological and endothelial markers such as CD45, CD34, CD14 or CD11b, CD79\(\alpha\) or CD19, as well as human leukocyte antigen (HLA)-DR [128; 154]. 3. MSCs can differentiate in vitro into osteoblasts, adipocytes, and chondroblasts [128]. As previously noted, the capacity of MSCs to differentiate into various cell lineages was a factor in their early designation as a form of stem cell and continues to be one of their defining traits [112]. Embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells are the three varieties of stem cells that are most frequently investigated in the context of stem cell treatment at present. ESCs are totipotent stem cells derived from a four- to five-day-old zygotic cell [156]. Producing embryonic stem cells has raised the most ethical concerns regarding their use [157]. Therefore, its use is restricted to biomedical research, and it remains illegal to use it to treat any disease. There is still a great deal of controversy about the significant moral challenges that come up whenever an embryo has to be destroyed to retrieve the ESCs [157; 158; 159]. iPSCs possess a high level of pluripotency while avoiding the ethical issues associated.