Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain.
Exp Cell Res. 2009 Dec 10;315(20):3598-610. doi: 10.1016/j.yexcr.2009.08.004. Epub 2009 Aug 15.
Mesenchymal stem cells (MSC) have been extensively studied and gained wide popularity due to their therapeutic potential. Spontaneous transformation of MSC, from both human and murine origin, has been reported in many studies. MSC transformation depends on the culture conditions, the origin of the cells and the time on culture; however, the precise biological characteristics involved in this process have not been fully defined yet. In this study, we investigated the role of p53 in the biology and transformation of murine bone marrow (BM)-derived MSC. We demonstrate that the MSC derived from p53KO mice showed an augmented proliferation rate, a shorter doubling time and also morphologic and phenotypic changes, as compared to MSC derived from wild-type animals. Furthermore, the MSC devoid of p53 had an increased number of cells able to generate colonies. In addition, not only proliferation but also MSC differentiation is controlled by p53 since its absence modifies the speed of the process. Moreover, genomic instability, changes in the expression of c-myc and anchorage independent growth were also observed in p53KO MSC. In addition, the absence of p53 implicates the spontaneous transformation of MSC in long-term cultures. Our results reveal that p53 plays a central role in the biology of MSC.
间充质干细胞（MSC）由于其治疗潜力而被广泛研究并受到广泛关注。许多研究报道了源自人和鼠的 MSC 的自发转化。MSC 的转化取决于培养条件、细胞的来源和培养时间；然而，涉及该过程的精确生物学特征尚未完全定义。在这项研究中，我们研究了 p53 在鼠骨髓（BM）来源的 MSC 生物学和转化中的作用。我们证明，与源自野生型动物的 MSC 相比，源自 p53KO 小鼠的 MSC 表现出更高的增殖率、更短的倍增时间以及形态和表型变化。此外，缺乏 p53 的 MSC 具有更多能够产生集落的细胞数。此外，不仅增殖，而且 MSC 分化也受到 p53 的控制，因为其缺失会改变该过程的速度。此外，p53KO MSC 还观察到基因组不稳定性、c-myc 表达的变化和非锚定依赖性生长。此外，p53 的缺失意味着 MSC 在长期培养中自发转化。我们的结果表明，p53 在 MSC 的生物学中发挥核心作用。
