Mesenchymal stromal cell senescence and apoptosis have been identified as critical molecular hallmarks in aging. In this study, we used stromal cell sheet culture as an in vitro model to study the progressive changes of cellular senescence, apoptosis and underlying mechanism in Wnt3a treated cells. Our results showed fresh bone marrow mesenchymal stromal cells (BMSCs) become senescent and undergo apoptosis with increased inflammatory profile and Reactive Oxygen Species (ROS) in high-density cell sheet cultures. The gene expression level of senescence related proteins and key regulators of apoptosis in cell sheet cultures was significantly increased in older BMSCs at Days 4 and 7 cultures compared with younger cells at Day 1 cultures. More importantly, Wnt signaling activation significantly reduced senescence in cell sheet cultures by direct regulation of cell cycle inhibitor p27. This study not only characterized the cellular and molecular features of aging stromal cells in short-term cell sheet cultures, but also identified the downstream target responsible for Wnt inhibition of cell senescence.

中文翻译：

---

Wnt 信号传导通过靶向细胞周期抑制剂 p27 抑制高密度细胞片培养诱导的间充质基质细胞衰老


间充质基质细胞衰老和凋亡已被确定为衰老的关键分子标志。在本研究中，我们使用基质细胞片层培养物作为体外模型来研究Wnt3a处理的细胞中细胞衰老、凋亡的进行性变化及其潜在机制。我们的结果显示，在高密度细胞片培养物中，新鲜骨髓间充质基质细胞（BMSC）会衰老并发生凋亡，炎症特征和活性氧（ROS）增加。与第 1 天培养的年轻细胞相比，第 4 天和第 7 天培养的老年 BMSC 中细胞片层培养中衰老相关蛋白和细胞凋亡关键调节因子的基因表达水平显着增加。更重要的是，Wnt 信号传导激活通过直接调节细胞周期抑制剂 p27 显着减少细胞片层培养物的衰老。这项研究不仅表征了短期细胞片层培养中衰老基质细胞的细胞和分子特征，而且还确定了负责 Wnt 抑制细胞衰老的下游靶点。