Upregulated heme oxygenase-1 expression of mouse mesenchymal stem cells resists to chemotherapy-induced bone marrow suppression

Background Bone marrow hematopoietic function suppression is one of the most common side effects of chemotherapy.After chemotherapy,the bone marrow structure gets destroyed and the cells died,which might cause the hematopoietic function suppression.Heme oxygenase-1 （HO-1） is a key enzyme of antioxidative metabolism that associates with cell proliferation and resistance to apoptosis.The aim of this study was to restore or resist the bone marrow from the damage of chemotherapy by the HO-1 expression of mouse mesenchymal stem cells （mMSCs） homing to the mice which had the chemotherapy-induced bone marrow suppression.Methods One hundred and sixty female Balb/c mice （6-8-weeks old） were randomly divided into four groups.Each group was performed in 40 mice.The control group was intraperitoneally injected for 5 days and tail intravenously injected on the 6th day with normal saline.The chemotherapy-induced bone marrow suppression was established by intraperitoneally injecting cyclophosphamide （CTX） into the mice which performed as the chemotherapy group.The mMSCs were tail intravenously injected into 40 chemotherapically damaged mice which served as the mMSCs group.The difference between the HO-1 group and the mMSCs group was the injected cells.The HO-1 group was tail intravenously injected into the mMSCs that highly expressed HO-1 which was stimulated by hemin.The expression of HO-1 was analyzed by Western blotting and RT-PCR.Cell proliferation was measured using the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay.Histopathologic examinations were performed 1 week after injection.Results Compared with the control group,the expression levels of HO-1 mRNA and protein were significantly higher in the HO-1 group （all P ＜0.05）,even obviously than the mMSCs group.CTX treatment induced apoptosis and inhibited proliferation.After injected,the white blood cell （WBC）,red blood cell （RBC） and platelet （PLT） declined fast and down to the bottom at the 7th day.The bone marrow structure was destroyed incomplete.In vitro,the survival rate of cells in chemotherapy group was less than 50％ after 24 hours.In contrast,mMSCs could do a favor to the cellular cleavage and proliferation.They slowed down the cell mortality and more than 50％ cells survived after 24 hours.The effects of blocking apoptosis and bone marrow recovery could be more effective in the HO-1 group.In the HO-1 group,it had observed that the bone marrow structure became complete and the hemogram clo