Mesenchymal stem cell-based cartilage regeneration approach and cell senescence: can we manipulate cell aging and function?

Aging is the most prominent risk factor triggering several degenerative diseases, such as osteoarthritis (OA). Due to its poor self-healing capacity, once injured cartilage needs to be reestablished. This process might be approached through resorting to cell-based therapies and/or tissue engineering. Human mesenchymal stem cells (MSCs) represent a promising approach due to their chondrogenic differentiation potential. Presently, in vitro chondrogenic differentiation of MSCs is limited by two main reasons as follows: aging of MSCs, which determines the loss of cell proliferative and differentiation capacity and MSC-derived chondrocyte hypertrophic differentiation, which limits the use of these cells in cartilage tissue regeneration approach. The effect of aging on MSCs is fundamental for stem cell-based therapy development, especially in older subjects. In the present review we focus on homeostasis alterations occurring in MSC-derived chondrocytes during in vitro aging. Moreover, we deal with potential cell aging regulation approaches, such as cell stimulation through telomerase activators, mechanical strain, and epigenetic regulation. Future investigations in this field might provide new insights into innovative strategies for cartilage regeneration and potentially inspire novel therapeutic approaches for OA treatment.