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

// Nils H. Nicolay 1,2,3 , Ramon Lopez Perez 2,3 , Rainer Saffrich 4 and Peter E. Huber 1,2,3 1 Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany 2 Heidelberg Institute for Radiation Oncology (HIRO), National Center for Radiation Research in Oncology, Heidelberg, Germany 3 Department of Molecular and Radiation Oncology, German Cancer Research Center (dkfz), Heidelberg, Germany 4 Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany Correspondence to: Nils H. Nicolay, email: // Keywords : mesenchymal stem cell, radiotherapy, double strand break, tissue regeneration Received : May 17, 2015 Accepted : May 30, 2015 Published : June 08, 2015 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.