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Abstract
Abstract Introduction 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. Methods 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. Results 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. Conclusion This study contributes insight into the nature of quercetin and its effects on in vitro MSC culture and function.
Highlights
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
Bone marrow-derived MSCs from male donors between 20 and 30 years old were bought from Lonza and cultured in a Examining the Effects of Quercetin on Phenotypic Characteristics of Human Mesenchymal Stem
The lack of senolytic effect was further suggested by the SAβ-gal staining, which only showed a reduction of senescent cells following quercetin treatment in donor 257
Summary
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. Methods The phenotypic, genotypic, and immunomodulatory effects of quercetin were assessed using in vitro models. Results Quercetin was not found to be beneficial to MSC function. Conclusion This study contributes insight into the nature of quercetin and its effects on in vitro MSC culture and function. BM-MSCs are the most widely utilized MSC owing to their relative ease of isolation and culture, abundance, and robust differentiation capability [3, 4]
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