Context: Our previous studies showed that mesenchymal stem cells (MSCs) preferentially migrated to irradiation-damaged thymus tissue to maintain the thymus integrity and simultaneously decrease the incidence of thymoma from 57 to 37.5%.
Objective: This study was designed to investigate the mechanisms by which MSCs decrease the irradiation-induced thymoma formation.
Materials and methods: Thymus genome DNA was extracted, treated with sulfite, and amplified by polymerase chain reaction (PCR) using bisulfite sequencing PCR (BSP) as primers. The PCR productions were sequenced after recovery from 1.5% agarose gel electrophoresis. These sequences were analyzed using ClustalW2-Multiple Sequence Alignment. p53 expression in thymus or thymoma was measured using immunohistochemistry.
Results: Study showed the p53 methylation in irradiation alone group took place at loci +143 and -1190, which are beyond known binding motif of transcription factors. However, Matlnspector Professional Database revealed that locus -1190 is located in binding region of E2A transcription factor. In the non tumor thymus tissues from MSCs-treated irradiated mice, p53 promoter methylation existed at four loci. Three loci of them located at either negative regulation regions or their vicinity. The methylation affects the interaction between transcription factors and p53 promoter to increase the expression of p53. Indeed, an increased p53 expression was detected by immunohistochemistry in thymus tissues from MSCs-treated irradiated mice as compared to irradiated alone mice.
Conclusion: MSCs decrease the incidence of irradiation-induced thymoma, which may be mediated by improving thymus microenvironment and changing the methylation of p53 promoter, and subsequently maintaining genome's stability.