p53 regulates the proliferation, differentiation and spontaneous transformation of mesenchymal stem cells

• Published in: Experimental cell research 2009-12, Vol.315 (20), p.3598-3610
• Main Authors: Armesilla-Diaz, Alejandro, Elvira, Gema, Silva, Augusto
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Antigens, Differentiation - metabolism; BONE MARROW; CALVES; Cell culture; Cell Differentiation - genetics; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cellular biology; Colony-Forming Units Assay; DNA-Binding Proteins - genetics; ESTERS; Gene Expression - genetics; Gene therapy; Genomic Instability - genetics; IODIDES; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; MICE; Mice, Inbred C57BL; Mice, Knockout; NEOPLASMS; Neoplasms - metabolism; Neoplasms - pathology; p53; POLYMERASE CHAIN REACTION; Polyploidy; Proteins; Proto-Oncogene Proteins c-myc - genetics; Rad51 Recombinase - metabolism; Rodents; Self-renewal and differentiation; STEM CELLS; TRANSCRIPTION; TUMOR CELLS; Tumor stem cells; Tumor Suppressor Protein p53 - physiology
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2009.08.004

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.