Nunes Allancer D C, Pitcher Louise E, Exner Henry A, Grassi Diego J, Burns Brittan, Sanchez Maria Beatriz Herrera, Tetta Ciro, Camussi Giovanni, Robbins Paul D
Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
Aelis Farma, Bordeaux, France.
Stem Cell Rev Rep. 2025 Apr 12. doi: 10.1007/s12015-025-10876-x.
Expansion of adult stem cells in culture increases the percent of senescent cells, reduces their differentiation capacity and limits their clinical use. Here, we investigated whether treatment with certain senotherapeutic drugs would reduce the accumulation of senescent cells during expansion of human liver stem cells (HLSCs) while maintaining their differentiation capacity. Our results demonstrate that chronic treatment with the senomorphic XJB-5-131 or the senolytics cocktail D + Q reduced the number of senescent cells and significantly reduced the expression of senescence-associated genes and several inflammatory SASP factors in later passage HLSCs. Additionally, treatment with XJB-5-131 and D + Q improved the capacity of HLSCs to undergo osteogenic differentiation following extensive in vitro expansion. Overall, our data demonstrate that treatment with XJB-5-13 or D + Q results in a reduction in the percentage of replication-induced senescent HLSCs and likely other types of adult stem cells and improve the potential therapeutic use of later passage human stem cells.
培养过程中成年干细胞的扩增会增加衰老细胞的比例，降低其分化能力，并限制其临床应用。在此，我们研究了使用某些衰老治疗药物进行处理是否会在人肝干细胞（HLSC）扩增过程中减少衰老细胞的积累，同时维持其分化能力。我们的结果表明，用衰老形态调节剂XJB-5-131或衰老溶解剂组合D+Q进行长期处理可减少衰老细胞数量，并显著降低传代后期HLSC中衰老相关基因和几种炎症性衰老相关分泌表型因子的表达。此外，用XJB-5-131和D+Q处理可提高HLSC在广泛体外扩增后进行成骨分化的能力。总体而言，我们的数据表明，用XJB-5-13或D+Q处理可降低复制诱导的衰老HLSC以及可能其他类型成年干细胞的百分比，并改善传代后期人干细胞的潜在治疗用途。
