Cell senescence: a challenge in cartilage engineering and regeneration

Cartilage defects, most commonly caused by aging and degenerative disease, have become the primary target of cartilage tissue engineering due to a lack of effective treatments and limited regenerative abilities. The limited success of autologous chondrocyte implantation necessitates the development of alternative cell sources. Adult mesenchymal stem cells (MSCs) with multiple lineage differentiation potentials from various sources can supplement the shortage of human autologous chondrocytes. However, cell senescence presents a big challenge for large-scale ex vivo expansion and maintenance of MSC stemness. In this review, we will summarize some potential factors resulting in cell senescence during cartilage tissue engineering, including ex vivo expansion, donor age, and degenerative diseases, and the challenge in the identification of senescent cells. The presence of senescence-associated β-galacotosidase and DNA damage, accumulation of reactive oxygen species, the decline of DNA replication and telomerase activity, and shortened telomere length is indicative of senescence, but none of them are specific. To some extent, growth factors, antioxidants, serum deprivation, or platelet-rich plasma treatment as well as low oxygen have been successful in retarding cell senescence. Recently, decellurized extracellular matrix, especially decellularized stem cell matrix, has emerged as a more promising tool in retaining cells in a younger state. Some potential signaling pathways in cell senescence will also be discussed for their potential involvement in cartilage regeneration despite the fact that comprehensive mechanisms are still under investigation.