Effect of cisplatin, topotecan, daunorubicin and hydroxyurea on human mesenchymal stem cells / 中国实验血液学杂志

ABSTRACT

Mesenchymal stem cells (MSC) are important cellular component of the bone marrow microenvironment in supporting hemopoiesis. Li J et al reported previously that MSCs are resistant to chemotherapy commonly used in hematologic malignancies but are relatively sensitive to anti-microtubule agents. However, the response of MSCs to other chemotherapeutic agents commonly used in solid tumour settings remains unknown. This study was purposed to evaluate the acute direct effects of 4 individual chemotherapeutic agents on human MSCs (hMSC), including cisplatin, topotecan, daunorubicin and hydroxyurea. Using an in vitro culture system, the chemosensitivity of hMSC was determined by XTT assay and compared with NB-4 cells and normal peripheral blood mononuclear cells (PBMNC). The recovery of cell numbers following exposure to chemotherapeutic agents and apoptosis induced by chemotherapy in hMSC were evaluated. The results showed that although hMSCs were more resistant to the 4 agents above mentioned than NB-4 cells, they were sensitive to topotecan, cisplatin and daunorubicin than PBMNCs. The IC₅₀ values of hMSCs for topotecan, cisplatin, hydroxyurea and daunorubicin were 636, 24.8, > 20 and 2.4 times of those of NB-4 cells respectively. The IC₅₀ values of human PBMNCs for topotecan, cisplatin and daunorubicin were > 27, 1.9 and 1.4 times of those of hMSCs respectively. Reduction of cell number was observed in hMSCs treated with the 4 drugs in clinically relative concentrations. Sustained suppression in hMSCs was observed following 3 days exposure to the 4 agents. It is concluded that the cisplatin, topotecan, daunorubicin and hydroxyurea alone can induce apoptosis of hMSCs and exert persistent suppressive effect on the proliferation of hMSCs even with short term exposure.