Effects of cytotoxic agents on proliferation and differentiation of mesenchymal stem cells from mouse lung and compact bone

BACKGROUND: During high-dose chemotherapy, cytotoxic agents have killing effects on tumor cells, and can damage normal cells, even stem cells, in tumor patients. OBJECTIVE: To study the influence of cytotoxic agents on proliferation and differentiation of mesenchymal stem cells (MSCs) derived from mice lung and compact bone. DESIGN, TIME AND SETTING: In vitro controlled cytologicai study was performed at the Room of Cell Biology, Institute of Basic Medical Sciences, Academy of Military Medical Sciences of Chinese PLA, and the Department of Oncology, General Hospital of Beijing Military Area Command of Chinese PLA from May 2007 to August 2008. MATERIALS: A total of 3 clean C57BL/6 mice aged 3-5 weeks were obtained from the Experimental Animal Center of Academy of Military Medical Sciences of Chinese PLA. METHODS: Adherent cells from digested lung and compact bone were cultured and expanded in 10% fetal bovine serum/a-MEM. These cells were identified as mesenchymal stem cells, and then examined in vitro using MTT assay to find out their sensitivity to cytotoxic agents, comprising myleran, adriamycin, cyclophosphamide, etoposide, methotrexate, vincristine and cis-diamminedichloroplatinum. Drug concentration range was set according to a reference. Cells in the blank control group were administered a-MEM containing 10% fetal bovine serum. After exposure to cytotoxic agents, the cells were induced to differentiate into adipocytes and osteoblasts. MAIN OUTCOME MEASURES: Growth inhibition, proliferation and differentiation of lung and compact bone-derived MSCs were measured following treatment of various drugs. RESULTS: Lung- and compact bone-derived MSCs were resistant to busulphan, cyclophosphamide and methotrexate and mildly sensitive to vincristine, etoposide, cis-diamminedichloroplatinum and adriamycin. The sensitivity to cyclophosphamide and myleran was similar between lung and compact bone-derived MSCs. However, the sensitivity to methotrexate, vincristine, etoposide and adriamycin was less in lung-derived MSCs compared with the compact bone-derived MSCs in mice. The sensitivity to cis-diamminedichloroplatinum was greater in lung-derived MSCs compared with the compact bone-derived MSCs in mice. Compared with blank control group, treatment of cyclophosphamide, myleran and methotrexate had small effects on proliferation of lung- and compact bone-derived MSCs. Within 24 hours of treatment of cyclophosphamide, myleran, methotrexate, vincristine and etoposide, l