# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 4 MSC-Based Therapy for OA
### Comparisons between Different Forms of MSCs  
The etiology of early-onset OA may be attributed to sporadic mutations occurring seldom in monogenetic disorders associated with OA. In contrast, late-onset OA is often characterized by a complex clinical manifestation encompassing prominent genetic differences and other risk factors [35]. Different sources of MSCs have unique characteristics and have their advantages and disadvantages. BM-MSCs were the first MSCs studied; however, due to their significant invasiveness and restricted availability inside living organisms, they have been replaced by MSCs obtained from other sources. BM-derived stromal cells are widely used as the primary clinical source of MSCs. The components above are obtained from a biological matrix consisting of hematopoietic stem cells, endothelial progenitor cells, and associated cytokines and growth factors [270]. Previous studies have used stromal cells obtained from adipose tissue as a viable alternative cell line. The production of stem cells in adipose tissue is comparatively greater. Furthermore, it has been shown that cells originating from adipose tissue have a higher lifespan than cells produced from bone marrow. The research conducted by [PERSON] et al. examined the disparity between these two cellular groups. The investigation findings indicated that over one year, adipose tissue-derived AD-MSCs showed a higher level of safety and consistent effectiveness in enhancing pain relief, functional improvement, and radiological results [270; 271]. The AD-MSCs exhibited inferior cell shape and matrix formation compared to BM-MSCs in the context of in vitro chondrogenesis. However, their ability to undergo adipogenic differentiation was shown to be similar. AD-MSCs have a high degree of genetic and morphological stability, making them particularly suitable for purposes. Furthermore, when subjected to a prolonged incubation period, these MSCs demonstrate superior proliferation capabilities. Due to their strong in vitro proliferation ability, low immunogenicity, simplicity of isolation and culture, and persistent multidirectional differentiation potential, UC-MSCs are often used. Examining gene expression demonstrated that BM-MSCs exhibit elevated levels of genes associated with osteogenic development compared to UC-MSCs [272]. Previous studies have shown that SM-MSCs have a superior capacity for chondrogenesis compared to MSCs produced from alternative tissue sources. The potential solution may be in the expression of growth differentiation factor 5 (GDF5), a factor often seen in articular cartilage. Nevertheless, there are ongoing issues with the enzymatic digestion process to isolate these cells [270]. iPSCs derived from human sources have distinct characteristics, including an augmented regeneration potential compared to traditional stem cells. Moreover, iPSC-MSCs possess the ability to modify extensively differentiated adult somatic cells via the use of genetic engineering techniques. In theory, it is possible to transform all adult somatic cells into iPSC-MSCs, which have been seen to possess a greater capacity for proliferation compared to traditional MSCs [272]. The IPFP is a noteworthy and auspicious reservoir of MSCs that effectively addresses OA. Research has shown that these MSCs had superior chondrogenic capabilities to those produced from bone marrow or subcutaneous fat [270]. UC, amniotic membrane, and fat sources exhibit greater accessibility and possess a better potential for proliferation, but the proliferative power of BM-MSCs is comparatively insufficient [272]. Regarding MSCs inside the tissue, the UC-MSCs have the greatest concentration, followed by the amniotic fluid and adipose tissue. In relation to the proliferation potential of MSCs, it is seen that UC-MSCs and amniotic-derived MSCs exhibit distinct advantages, followed by AD-MSCs and BM-MSCs.