Stem cell transfusion restores immune function in radiation-induced lymphopenic C57/BL6 mice.

Radiation-induced lymphopenia (RIL) is associated with treatment of different tumors (lung, colon, pancreas, breast, sarcomas and glioblastoma). It is a significant clinical problem affecting the survival of cancer patients. The biological mechanisms leading to RIL are not clearly understood. In this study, we established a mouse model of RIL representing therapeutic clinical regimen for lung cancer. Flow cytometry was used to analyze circulating levels of T and B cells and bone marrow (BM) stem cells. We found that fractionated radiation to the thorax significantly reduced circulating T and B cells as well as BM stem cells. Ex-vivo irradiation of blood and autologous reinjection to mice also significantly induced lymphopenia. Furthermore, we found that mobilization of stem cells from the BM and autologous stem cell transplant rescued RIL in mice.
Overall our results suggest that RIL through not only direct effect on circulating lymphocytes, but also through indirect effect on circulating lymphocytes as well as stem cells in the non-irradiated BM. These results open a new window for investigating the direct and indirect biological mechanisms leading to RIL, and provide a preclinical basis to test the effect of stem cell transplantation for treatment of RIL in cancer patients.