# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 4 MSC-Based Therapy for OA
### Sources of MSCs
#### 4.2.1 BM-MSCs for OA Therapy  
Because of their accessibility, rapid cell proliferation, long-term differentiation capabilities, and minimal immunological exclusion, BM-MSCs are the most widely employed source of therapeutic MSCs [191]. Numerous studies have established acceptable clinical outcomes in patients with knee OA who underwent either intra-articular injection or the surgical implantation of autologous BM-MSCs [144; 192; 193]. BM-MSCs have a wide range of properties that are likely to be helpful in treating genetic, mechanical, and age-related deterioration in illnesses such as OA [194]. BM-MSCs have immunomodulatory capabilities due to significantly limiting the proliferation of inflammatory T cells, monocytes, and dendritic cells via direct cell-to-cell contact. They also release anti-inflammatory mediators such as PGE-2, IDO, IL-1 Ra, and IL-10 [194; 195]. These cells affect the local OA microenvironment by activating chondrogenic progenitor cells and promoting their maturation into mature chondrocytes through the production of BMPs and TGF1 [196]. When differentiation indicators such as BMP-7 and TGF-1 are utilized, it is well documented that BM-MSCs develop in vitro into chondrocytes. Differentiation of BM-MSCs into chondrocytes in vitro has been demonstrated using differentiation cues such as BMP-7 and TGF-1. A similar method could be used to differentiate BM-MSCs in vivo. By raising the amounts of BMP-7 and TGF-1 in the local joint environment, BM-MSCs can develop into chondrogenic progenitor cells (CPCs) in vivo, mediated by changes in the expression of master regulatory genes such as Sox9, homeobox A (HoxA), HoxD, and Gli3. Chondroblasts, which are unequivocally increased for collagen types II B, IX, and XI, develop from CPCs. The CPCs then mature into mature chondrocytes under the control of balanced collagen X (Col X) expression and release collagen II, which is made up of sulphated GAG (sGAG) building blocks and helps maintain the structural integrity of hyaline cartilage [197]. Collagen X overexpression has been linked to chondrocyte hypertrophy and fibrous cartilage synthesis; hence, the regulated expression of Col X would likely result in hyaline cartilage deposition [198]. While BM-MSCs have many advantages, they also have certain drawbacks. The donor factors, such as disease severity and age, significantly impact the yields and the capacity for differentiation and repair [199]. MSCs only make up 0.001-0.01% of the cells in the BM, which makes things even more complicated [199; 198]. Furthermore, the risk of infection during the separation of BM cells cannot be discounted. This procedure can be performed under local anesthesia and guided by ultrasound or fluoroscopic imaging to improve accuracy [200; 201]. The first clinical trial of BM-MSCs transplantation for the treatment of articular cartilage abnormalities was conducted nearly two decades ago. The study comprised 24 patients with high tibial osteotomy-related knee OA, with half getting autologous BM-MSCs transplantation and the other half serving as controls. Metachromasia was identified in most of the examined tissue regions after 42 weeks, with partial presence of tissue resembling hyaline cartilage. The cell-transplanted group had substantially better arthroscopy and histology grading scores than the cell-free control group, suggesting that transplantation of BM-MSCs has promise as a therapeutic approach for osteoarthritis [202; 203; 204]. In 2008, [PERSON] and colleagues described a patient who received a percutaneous injection of BM-MSCs and reported significant cartilage growth, reduced discomfort, and improved joint mobility. They then presented a case study of 339 patients, revealing that after MSC therapy, only 6.9 percent of patients who needed total knee replacement surgery (69 percent of the patient group) required replacement surgery again. At 11 months, 60 percent of patients reported more than 50% pain relief, whereas 40% reported more than 75% [205].