Maier, P., Herskind, C., Fleckenstein, K., Spier, I., Laufs, S., Jens Zeller, W., Fruehauf, S. and Wenz, F. MDR1 Gene Transfer Using a Lentiviral SIN Vector Confers Radioprotection to Human CD34 Hematopoietic Progenitor Cells. Radiat. Res. 169, 301–310 (2008).

Tumor radiotherapy with large-field irradiation results in an increase in apoptosis of the radiosensitive hematopoietic stem cells (CD34 ). The aim of this study was to demonstrate the radioprotective potential of MDR1 overexpression in human CD34 cells using a lentiviral self-inactivating vector. Transduced human undifferentiated CD34 cells were irradiated with 0–8 Gy and held in liquid culture under myeloid-specific maturation conditions. After 12 days, MDR1 expression was determined by the rhodamine efflux assay. The proportion of MDR1-positive cells in cells from four human donors increased with increasing radiation dose (up to a 14-fold increase at 8 Gy). Determination of expression of myeloid-specific surface marker proteins revealed that myeloid differentiation was not affected by transduction and MDR1 overexpression. Irradiation after myeloid differentiation also led to an increase of MDR1-positive cells with escalating radiation doses (e.g. 12.5–16% from 0–8 Gy). Most importantly, fractionated irradiation (3 × 2 Gy; 24-h intervals) of MDR1-transduced CD34 cells resulted in an increase in MDR1-positive cells (e.g. 3–8% from 0–3 × 2 Gy). Our results clearly support a radioprotective effect of lentiviral MDR1 overexpression in human CD34 cells. Thus enhancing repopulation by surviving stem cells may increase the radiation tolerance of the hematopoietic system, which will contribute to widening the therapeutic index in radiotherapy.