Abstract:
To investigate the effect of the Wnt5a-modified bone mesenchymal stem cells (bMSCs) on hemopoiesis and leukemic cell growth of mice with acute myeloid leukemia. Methods: A human leukemia model with severe combined immunodeficiency (SCID) was intravenously inoculated with HL60 cells. Wright staining on the peripheral blood and identification using a bone marrow flow cytometry were performed. The well-modeled mice were divided into four groups: the experimental group (Group A, Ad5-Wnt5a-bMSCs + model mice) and the control groups (Group B, Ad5-GFP-bMSC+ model mice; Group C, bMSC+ model mice; and Group D, model mice).The exogenous Wnt5a-modified bMSCs were transplanted into the leukemia mouse model through the marrow cavity, and the colonization was detected using RT-PCR . Changes in the leukemia cells and marrow hemopoiesis in peripheral blood, bone marrow, liver, spleen, and kidney before and after transplantation were determined using histocytochemistry, RT-PCR, flow cytometry, histopathology, bone marrow MSC, and CFU-Mix culture. Results: A model of acute myeloid leukemia was successfully established. The exogenous Wnt5a gene was successfully transfected into bMSCs at a transfer rate of 36.8% and into the bone marrow of the receptors. After the transplantation, the SCID mice in the experimental group exhibited significantly higher survival rates ( P < 0.05 ) and significantly lower nucleated cell and tumor cell counts in the peripheral blood ( P < 0.05 ) compared to the control group. Furthermore, the CFU-Mix and MSC colony growth and recovery were faster. The number of colonies was significantly higher ( P < 0.05 ), and the positive rate of CD33 expression in the bone marrow, lung, liver, spleen, and other organs in the experimental group was considerably lower ( P < 0.05 ). Conclusion: The Wnt5a-modified bMSCs can effectively inhibit the growth of leukemia cells in vivo and support bone marrow hemopoiesis.