The maintenance of genetic stability of embryonic and induced pluripotent stem cells during anticancer therapies

Abstract

Regenerative medicine is a very rapidly developing discipline. Its progress contributes to elongated life expectancy and improved quality of life of patients suffering from so far incurable diseases. Stem cells (SCs) are undifferentiated cells that are able to undergo unlimited number of cell divisions and differentiation into specialized cells. Therapies based on SCs constitute a relatively new and promising approach in regenerative medicine. Radiotherapy is the most often used method in the treatment of cancer. In the future, the usage of SCs will be connected with the inevitable exposure of SCs to ionizing radiation during both treatment and diagnosis. The issue of genetic stability of SCs and cells differentiated from them is crucial, particularly regarding the application of these cells in clinical practice. It is important to emphasize that differentiated and undifferentiated cells possess different cell cycle, metabolism, initial level of reactive oxygen species, DNA repair mechanisms, susceptibility to apoptosis and frequency of mutations. All these factors contribute to the distinct radiosensitivity of SCs and differentiated cells. The aim of this study was to present the latest literature data concerning DNA repair mechanisms in pluripotent SCs (Homologous Recombination, Non-homologous End Joining, Mismatch Repair, Base Excision Repair and Nucleotide Excision Repair) in response to the influence of cyto- and genotoxic agents, such as ionizing radiation and chemotherapeutics. Evaluation the efficacy of DNA repair mechanisms is relevant for pluripotent SCs, because ineffective DNA repair mechanisms may result in the accumulation of mutations and, consequently, to cancer.