# 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
A cohort of 30 individuals with chronic knee pain, unresponsive to traditional treatment methods, demonstrated significant improvements in several functional measures and cartilage integrity after receiving intra-articular injections of BM-MSCs [206]. [PERSON] et al. [207] revealed their findings on the use of autologous BM-MSCs for OA therapy (n = 4) in 2011. They injected approximately 8 to 9 106 cells into the knee cavities of patients. They discovered that it shortened the time it took for pain to emerge while walking, and that patients' visual analog scale (VAS) scores dropped from 8090 to 4565. They were unable to identify any improvement in X-rays, though. This trial was prolonged to five years following treatment, and researchers discovered that the beneficial effects of BM-MSCs began to fade after six months. Still, they remained significantly better at five years compared to baseline [144]. In 2013, [PERSON] et al. carried out a clinical study on osteoarthritis (n = 12). During this study, they injected 4107 BM-MSCs into the knee joints of patients with a Kellgren and Lawrence (KL) grade of 2-4. They found that the pain was relieved within three months and continued to improve for at least a year. Additionally, the Lequesne and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) ratings improved significantly. In addition, the quantitative MRI data on cartilage quality demonstrated an increase over the previous two years [192]. Additionally, the same research team reported a study in 2016 employing 4107 BM-MSCs to treat KL grade 2-3 OA. The findings of this study were reported in the journal Cell Reports. The daily activities VAS score was around 58.27 at the baseline visit, but it dropped to 19.47 at the one-year follow-up, and it further declined to 14.62, 14.93 at the four-year follow-up, with no severe adverse effects being recorded [208]. In 2014, [PERSON] et al. conducted a double-blind, randomized controlled study (RCT) to assess the efficacy and safety of intra-articular injections of allogeneic BM-MSCs in individuals with OA of the knee who had undergone partial medial meniscectomy. In 18 patients who received 50,106 BM-MSCs and 18 patients who received 150,106 BM-MSCs, there were indications of meniscus regeneration and a considerable reduction in knee pain compared to 18 control patients who did not get an injection [209]. In 2015, [PERSON] et al. randomly allocated 30 patients with knee OA to one of two treatment groups: 15 received intra-articular injections of 40,106 allogeneic human BM-MSCs and 15 received intra-articular injections of HA [206]. Patients treated with BM-MSCs reported a significant reduction in knee discomfort, an improvement in knee function, an increase in cartilage quality in post-treatment MRI defects, and no adverse effects. [PERSON] et al. investigated the efficacy and safety of intra-articular injections of allogeneic human BM-MSCs in knee OA patients. Sixty OA patients were randomized to receive 25, 50, 75, or 150,106 BM-MSCs or no BM-MSCs. The dosage of 25,106 BM-MSCs was the most effective for alleviating OA knee pain, with no significant side effects [210]. [PERSON] et al. [211] released their research on using 1, 10, or 50 million BM-MSCs to treat KL grade 3-4 OA in 2019. They found that neither the morphological cartilage scores nor the T2 relaxation levels increased. Using cartilage catabolic markers, they did show putative chondrocytes benefits at 50 million BM-MSCs dosages. In addition, they discovered that the therapy lowered the levels of pro-inflammatory CD14+ CD16+ monocyte/macrophage maker and pro-inflammatory IL-12p40 in synovial fluid.