# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 4 MSC-Based Therapy for OA
### General Characteristics
The shift of iPSC research from the laboratory to the clinic has been accompanied by several hurdles, including genomic instability, immunogenicity, teratoma development, and clonal diversity among iPSCs derived from the same donor cells. Consequently, the clinical safety of their use is of grave concern [160; 161]. Adult stem cells are typically located in cells that have undergone differentiation after birth and become specialized in a particular tissue. They are separated into two categories: hematopoietic stem cells (also known as HSCs) and MSCs [159]. The regeneration of adult stem cells is considered a relatively recent breakthrough that has shown promising results when applied to the treatment of several chronic degenerative illnesses. Adult stem cells are both risk-free and effective in treating a substantial number of distinct diseases and circumstances in some studies [162; 163]. _HCSs_ are the precursors of all types of blood cells, including erythrocytes, leukocytes, and platelets [164; 165]. HSCs, which may be found in the BM and the UC, are currently being used as a treatment for the majority of the disorders that affect blood cells [166]. _MSCs_ are multipotent stem cells that can be found throughout the musculoskeletal system of the human body. These cells have the ability to differentiate into a variety of osteoblasts, chondrocytes, adipocytes, astrocytes, and cardiomyocytes through a process known as cell differentiation. They can adhere rapidly to the plastic surfaces of the tissue culture plates [167]. MSCs offer numerous benefits for therapeutic applications that are not shared by other forms of stem cells. MSCs are preferred over other types of stem cells for therapeutic purposes due to a number of benefits, including their relatively high abundance, ease of separation, multilineage differential potential, decreased risk of malignant transformation, immunomodulatory capabilities, and absence of ethical concerns [168]:  
_Possibility of isolation and abundance._ MSCs can be extracted from a number of tissues throughout the body since they originate in the perivascular niche, including BM, adipose tissue, peripheral blood, the placenta, and the UC [169; 170]. _Diverse lineage possibilities._ MSCs can differentiate into numerous unique cell types. In addition to osteoblasts, chondrocytes, and adipocytes, researchers have successfully induced MSC differentiation into oligodendrocytes [169], insulin-producing cells [170; 171], and cardiomyocytesytes [172; 173; 174]. _Reduced risk of malignant transformation_. MSCs are endogenously engineered to have a limited capacity for proliferation in culture before entering a state of senescence, which prevents them from dividing [175]. Immunomodulatory properties.MSCs also have immunomodulatory properties, generating anti-inflammatory cytokines that inhibit adaptive and innate immune responses, enabling them to be used as universal donor cells without immunosuppressive [176; 177]. No ethical problems exist.MSCs can be derived from any tissue in the body, unlike ESCs, and hence do not present the ethical concerns associated with ESCs. Due to their high degree of pluripotency, ESCs have garnered considerable interest, but their use in therapeutic applications remains controversial due to safety concerns regarding the production of teratomas and ethical issues involving source animals [178]. There have been concerns expressed about the utilization of MSCs because of the following:  
In vitro modificationMass may be manipulated to create serum-derived agents such as viruses and prions during in vitro cultivation. The administration of these medications to individuals with OA may be harmful [179]. Due to these issues, there is an excellent demand for responsible cultural practices. Immunogenicity lossDue to the expression of the major histocompatibility complex II (MHCII) gene, MSCs may lose their immunosuppressive features upon differentiation. This issue is brought up by allo- and xenotransplantation.