A significant obstacle to mesenchymal stem cell (MSC) potency and therapeutic utility is in vitro senescence, an irreversible cessation of replication associated with age-related complications. Senolytic drugs, such as quercetin, may be helpful in selectively culling senescent cells while leaving non-senescent cells unaffected, thereby increasing potency of high-passage MSCs. The phenotypic, genotypic, and immunomodulatory effects of quercetin were assessed using in vitro models. Senescent cells, created through repeated subculturing of MSCs in vitro, and non-senescent cells were treated with 10 μM quercetin, differentiated into osteocytes, adipocytes, and chondrocytes, and analyzed to observe the effect of quercetin. Quercetin was not found to be beneficial to MSC function. It did not exhibit a consistent senolytic effect as evidenced by SAβ-gal and live dead staining, hindered proliferation in the short term in some donors, and lowered the expression of osteogenic markers COL1A1 and ALP. Quercetin treatment did not, however, negatively affect adipogenesis, chondrogenesis, or indoleamine 2,3 dioxygenase secretions. This study contributes insight into the nature of quercetin and its effects on in vitro MSC culture and function.
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