Mesenchymal stem cells (MSC) have the potential to revolutionize medicine by enabling regenerative therapies. These cells, derived from bone marrow, are multipotent and can differentiate into various cell types, including cartilage, bone, muscle, tendon, and adipose tissue. Unlike other cells, MSCs avoid allogeneic rejection in humans and in animal models, which is a major challenge in regenerative medicine. This review explores the mechanisms by which MSCs evade immune rejection, including their hypoimmunogenic nature, modulation of T cell function, and the creation of an immunosuppressive local environment. MSCs lack MHC class II expression and do not express co-stimulatory molecules necessary for T cell activation. They also inhibit T cell proliferation and modulate dendritic cell function, which is crucial for immune responses. Additionally, MSCs secrete soluble factors such as prostaglandins and interleukin-10, which contribute to an immunosuppressive environment. These mechanisms are similar to those observed in maternal tolerance of the fetal allograft and tumor immune evasion. MSCs are highly regulated and self-renewing, making them promising candidates for regenerative medicine. Despite their ability to avoid rejection, the exact mechanisms by which MSCs achieve this remain under investigation. The review highlights the potential of MSCs in regenerative medicine and the need for further research to fully understand their immunomodulatory properties.Mesenchymal stem cells (MSC) have the potential to revolutionize medicine by enabling regenerative therapies. These cells, derived from bone marrow, are multipotent and can differentiate into various cell types, including cartilage, bone, muscle, tendon, and adipose tissue. Unlike other cells, MSCs avoid allogeneic rejection in humans and in animal models, which is a major challenge in regenerative medicine. This review explores the mechanisms by which MSCs evade immune rejection, including their hypoimmunogenic nature, modulation of T cell function, and the creation of an immunosuppressive local environment. MSCs lack MHC class II expression and do not express co-stimulatory molecules necessary for T cell activation. They also inhibit T cell proliferation and modulate dendritic cell function, which is crucial for immune responses. Additionally, MSCs secrete soluble factors such as prostaglandins and interleukin-10, which contribute to an immunosuppressive environment. These mechanisms are similar to those observed in maternal tolerance of the fetal allograft and tumor immune evasion. MSCs are highly regulated and self-renewing, making them promising candidates for regenerative medicine. Despite their ability to avoid rejection, the exact mechanisms by which MSCs achieve this remain under investigation. The review highlights the potential of MSCs in regenerative medicine and the need for further research to fully understand their immunomodulatory properties.