Radio-resistant mesenchymal stem cells: mechanisms of resistance and potential implications for the clinic

Abstract

Mesenchymal stem cells (MSCs) comprise a heterogeneous population of multipotent stromal cells and can be isolated from various tissues and organs. Due to their regenerative potential, they have been subject to intense research efforts, and they may provide an efficient means for treating radiation-induced tissue damage. MSCs are relatively resistant to ionizing radiation and retain their stem cell characteristics even after high radiation doses. The underlying mechanisms for the observed MSC radioresistance have been extensively studied and may involve efficient DNA damage recognition, double strand break repair and evasion of apoptosis. Here, we present a concise review of the published scientific data on the radiobiological features of MSCs. The involvement of different DNA damage recognition and repair pathways in the creation of a radioresistant MSC phenotype is outlined, and the roles of apoptosis, senescence and autophagy regarding the reported radioresistance are summarized. Finally, potential influences of the radioresistant MSCs for the clinic are discussed with respect to the repair and radioprotection of irradiated tissues.

Keywords: double strand break; mesenchymal stem cell; radiotherapy; tissue regeneration.

Figure 1. Schematic depiction of signaling molecules and pathways involved in the sensing of DNA double strand breaks

Figure 2. Central pathways and proteins involved in the repair of radiation-induced DNA double strand breaks

NHEJ: non-homologous end joining; DSB: double strand break; HR: homologous recombination; dHJ: double Holliday junction.