MSCs reside in hypoxic niches within the bone marrow and tumour microenvironments. Irradiated mouse MSCs could withstand IR-induced apoptosis continued to proliferate and could differentiate along mesenchymal-derived lineages. Multiple DDR mechanisms synergistically contributed to MSC radio-resistance: robust DDR initiation DNA damage checkpoint activation and efficient DNA DSB repair. In this study, the role of the DDR in mediating mouse MSC radio-resistance was investigated. The DNA Damage Response (DDR) represents a network of signalling pathways that enable cells to activate biological responses to genotoxic stress, including DNA DSBs. Ionising radiation (IR) negatively impacts on cell survival largely due to the generation of DNA lesions, particularly of highly genotoxic DNA double-strand breaks (DSBs). The mechanisms that drive MSC radio-resistance are poorly understood. Mesenchymal stromal cells (MSCs) are radio-resistant stem cell progenitors that support haematopoiesis in the bone marrow and contribute to the tumour microenvironment.
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