Research On The Therapeutic Effect Of Cytokine And Hematopoietic Stem Cell Transplant In Radiation Injury

Objective: To examine the therapeutic effect of combined administration of rhIL-11 and rhG-CSF on acute radiation syndrome in beagles; To establish hOSM transgenic cell line and observe its effect on the proliferation of UCB CD34⁺ HSPC as a feeder layer.Methods:1) The model of acute radiation syndrome was established by 4.5 Gy ⁶⁰Coγray. The animals were subcutaneously administered rhIL-11 and rhG-CSF besides active symptomatic treatment. Hemogram of peripheral blood, pristine apoptosis and necrosis ratios of nucleated cell, the level of IL-2 and IFN-γin plasm and formation of bone marrow were used to evaluate the therapeutic effect. 2) hOSM transgenic cell line was established by molecular biology method and CD34⁺ HSPCs were separated by magnetic-activated cell sorting. After co-culture, the amplification effect was evaluated by flow cytometry. Then CD34+ cells stained by CFDA SE were injected into the SCID mice with sublethally irradiation and the effect of transplation was observed by fluorescence microscopy and RT-PCR.Results: 1) The survival rate of 45 days after exposure was increased and hemogram of peripheral blood was improved significantly. The rates of pristine apoptosis and necrosis of nucleated cell declined obviously. Early, the concentration of both IL-2 and IFN-γin plasm was up significantly, then the concentration of IL-2 rapidly descended, but that of IFN-γwas relatively stabile; 2)After 7 days'co-culture, the number of CD34+ cells increased by 9.6 times and the expression rate of homing-ralated molecules was still higher than 50%. Four weeks after transplantion, CD34+ cells were found in bone marrow of SCID mice. But the number of CD34+ HSPC incresed to the biggest after 14 days'co-culture. Conclusion: The combined administration of rhIL-11 and rhG-CSF significantly improved the recovery of hematopoietic and immunological function and hOSM transgenic cell line as a feeder layer can effectively amplify UCB CD34+ HSPC ex vivo and suppress its differentiation.