# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 4 MSC-Based Therapy for OA
### Sources of MSCs
#### 4.2.2 AD-MSCs for OA Therapy  
In 2001, human AD-MSCs were recognized as a potential reservoir of mesenchymal stem cells (MSCs) owing to their ease of access, abundant supply, and immunosuppressive characteristics. AD-MSCs can be obtained in substantial quantities and concentrated to a greater extent (about 500 times more) than BM-MSCs by simple approaches and with the use of local anesthetic. Furthermore, the differentiation potential of AD-MSCs is less influenced by the donor's age, as shown by previous studies [212; 213; 214]. AD-MSCs may be isolated from various human body sites [214]; however, AD-MSCs isolated from different areas have different characteristics [215]. AD-MSCs can be isolated from the upper arm, medial thigh, buttocks, trochanter, superficial deep abdominal depots, and even the IPFP of the knee joint. The stromal vascular fraction (SVF) comprises 2 to 6 million cells and can be retrieved in 1 mL lipoaspartate [192]. The number of AD-MSCs in one gram of AD-MSCs can range from 5000 to 200,000 [193; 203]. In other words, we could extract between 0.5 and 20 million AD-MSCs from 100 g of AD-MSCs from a patient. AD-MSCs can differentiate into adipocytes, osteoblasts, chondrocytes, and endothelial cells due to their mesodermal origin. In addition, it has been demonstrated that they can grow into cells of ectodermal and endodermal origin, such as vascular smooth muscle cells, keratinocytes, hepatocytes, beta-islet cells, neuron-like cells, and glial lineages [216; 217; 218; 219]. The most frequent procedure for isolating AD-MSCs is the enzymatic breakdown of fat tissue [152; 220]. Adipose tissue SVF including AD-MSCs and other endothelial and hematopoietic cells is removed using an enzyme (collagenase, dispase, or trypsin) [221]. AD-MSCs are described as plastic-adherent, cultured, multipotent cell populations that have undergone serial passages. In addition, some non-enzymatic digesting methods, such as centrifugation and filtering, are occasionally used. However, it should be noted that the yield range is relatively extensive. Numerous clinical studies conducted in recent years have shown the efficacy of AD-MSCs in therapeutic applications. [PERSON] et al. found that non-expanded SVF isolated from adipose tissue and processed in PRP resulted in notable improvements in pain score and cartilage layer thickness in 21 patients with grade II and III OA [222]. [PERSON] et al. investigated the efficacy and safety of intra-articular injections of autologous human AD-MSCs in patients with knee OA in phase I and phase II clinical studies. In phase I, three patients were administered 1107, 5107, and 1108 AD-MSCs, whereas, in phase II, nine patients received a high dose of 1 108 AD-MSCs [223]. Patients who received 1108 AD-MSCs reported decreased OA knee pain, improved knee function, hyaline-like cartilage regeneration in articular cartilage defects, and no severe adverse effects. Eighteen patients with symptomatic and severe knee OA were administered autologous AD-MSCs at three different doses: low (2106 cells), medium (10,106 cells), and high (50,106 cells). Six-month follow-up revealed no clinically significant adverse effects, and patients treated with low-dose AD-MSCs experienced substantial pain relief and functional enhancement [224]. [PERSON]'s research showed that the treatment of OA knees with 14.1 million viable, nucleated SVF cells resulted in a statistically significant improvement in WOMAC and VAS ratings, which remained stable after one year [225]. A clinical study evaluated the efficacy of AD-MSCs to that of microfracture alone in treating moderate to severe knee OA in 80 patients aged 18 to 50 years old. Following 24 months, the group that received treatment with AD-MSCs exhibited heightened signal intensity about tissue repair and improved knee injury and osteoarthritis outcome scores (KOOS) concerning pain and symptoms. However, no notable variances were observed in other sub-scores, including daily living activity, sports and recreation, and quality of life.