Abstract：
In equine regenerative medicine using bone marrow-derived mesenchymal stem/stromal cells (BM-MSC), the importance of the quality management of BM-MSC has been widely recognized. However, there is little information concerning the relationship between cellular senescence and the stemness in equine BM-MSC. In this study, we showed that stemness markers (NANOG, OCT4, SOX2 and telomerase reverse transcriptase) and colony forming unit-fibroblast apparently decreased accompanied with incidence of senescence-associated β-galactosidase-positive cells by repeated passage. Additionally, we suggested that down-regulation of cell proliferation in senescent BM-MSC was related to increased expression of cyclin-dependent kinase inhibitor 2B (CDKN2B). On the other hand, forced expression of NANOG into senescent BM-MSC brought upregulation of several stemness markers and downregulation of CKDN2B accompanied with restoration of proliferation potential and osteogenic ability. These results suggested that expression of NANOG was important for the maintenance of the stemness in equine BM-MSC.
摘要：
在使用骨髓间充质干细胞/基质细胞（BM-MSC）的马再生医学中，BM-MSC质量管理的重要性已得到广泛认可。然而,关于马BM-MSC细胞衰老与干性之间关系的信息很少。在这项研究中,我们显示了干性标记(NANOG，OCT4，SOX2和端粒酶逆转录酶）和集落形成单位成纤维细胞明显减少，伴随着衰老相关的β-半乳糖苷酶阳性细胞的重复传代。此外,我们提示衰老BM-MSC细胞增殖的下调与细胞周期蛋白依赖性激酶抑制剂2B(CDKN2B)的表达增加有关.另一方面,NANOG在衰老BM-MSC中的强制表达导致几种干性标志物的上调和CKDN2B的下调，伴随着增殖潜力和成骨能力的恢复。这些结果表明，NANOG的表达对于马BM-MSC的干性的维持很重要。
