Mesenchymal stromal cells: Radio-resistant members of the bone marrow

Mesenchymal stromal cells (MSCs) are multi-potent adult stem cells located in various tissues, including the bone marrow. MSCs are key components of the haematopoietic stem cell (HSC) niche within the bone marrow where they function to maintain haematopoietic homoeostasis by regulating HSC self-renewal and function. Bone marrow exposure to ionising radiation causes rapid depletion of radio-sensitive HSCs and their progenitors, leading to haematopoietic failure. However, host-/patient-derived MSCs can survive radiation doses lethal to the haematopoietic system. The mechanisms underlying MSC radio-resistance are currently under intense investigation. Here, we review the current knowledge of MSC radio-biology. The DNA damage response (DDR) represents an orchestrated network of signalling pathways that enable cells to respond to genotoxic damage. We discuss in detail the emerging importance of the DDR in mediating MSC radio-resistance and examine the DDR of MSCs in the context of other stem cell types. Finally, we examine future advances in understanding MSC radio-resistance and discuss the potential impact of the radio-resistance of these stem cells for the clinic.