Senescent Mesenchymal Stem Cells, a Target for Treating Age-Related Joint Disorders

Senescent cells accumulate in tissues throughout the body, and their collective signaling is pro-inflammatory to a significant degree. Focusing on cellular senescence in specific cell populations, such as stem cells or other critical cells in joint tissues, is a popular area of study. Adding senescent cells to a joint in mice produces degeneration, but specifically removing senescent cells from a joint using a locally injected senolytic drug doesn't reverse degeneration in humans. This suggests that the rest of the senescent cell population in the body can continue to provide enough signaling to the joint to maintain dysfunction. Nonetheless, a fair number of papers continue to look at the contribution of cells local to the issue in joint tissue.

Mesenchymal/medicinal stem/signaling cells (MSCs), well known for regenerative potential, have been involved in hundreds of clinical trials. Even if equipped with reparative properties, aging significantly decreases their biological activity, representing a major challenge for MSC-based therapies. Age-related joint diseases, such as osteoarthritis, are associated with the accumulation of senescent cells, including synovial MSCs. An impaired ability of MSCs to self-renew and differentiate is one of the main contributors to the human aging process.

Moreover, senescent MSCs (sMSCs) are characterized by the senescence-messaging secretome (SMS), which is typically manifested by the release of molecules with an adverse effect. Many factors, from genetic and metabolic pathways to environmental stressors, participate in the regulation of the senescent phenotype of MSCs. To better understand cellular senescence in MSCs, this review discusses the characteristics of sMSCs, their role in cartilage and synovial joint aging, and current rejuvenation approaches to delay/reverse age-related pathological changes, providing evidence from in vivo experiments as well.


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