Objective:To study the effects of busulfan(BS)pre-conditioning regimen and hPBMC transplantation amount on the humanized M-NSG mouse model of acute graft versus host disease(aGVHD).Methods:The humanized aGVHD model of immune-deficient mice,M-NSG mice,was induced by BS pre-conditioning and the transplantation amount of 1×107 cells/mouse and 5×107 cells/mouse,respectively.The clinical signs,survival rate,chimerism rate of human T cells,and target organ injury were observed.The effects of BS pre-conditioning and the transplantation amount of hPBMC on the established humanized aGVHD mouse model were compared.Results:The typical histopathological changes of target organs of aGVHD were found in the histopathological examination of each dose group of hPBMC transplantation.When the transplantation level of hPBMC 5×107 cells/animal was used,no significant effect was found in the overall survival period,clinical signs and body weight changes among the animals with BS pre-conditioning as compared to the non-conditioning group.When the transplantation level of hPBMC 1×107 cells/animal was used,the survival period of aGVHD model was significantly shortened in animals with BS pre-conditioning,and the appearance time of aGVHD-related clinical signs and body weight loss were earlier and more serious,respectively.No significant changes were found in the infiltration percentage of human T cells in peripheral blood of M-NSG mice with BS pre-conditioning.The survival period of M-NSG mice,clinical signs,body weight changes,and the chimerism rate of human T cells(CD+3 CD+8)were significantly correlated to the amount of hPBMC transplanted.Conclusion:Both the amount of hPBMC transplanted and BS pre-conditioning regimen can aggravate the performance of the humanized aGVHD mouse model.Therefore,the use of BS combined with lower dose hPBMC can realize the establishment of humanized aGVHD mouse model,which provides a reliable preclinical model for the study of the mechanism of aGVHD.
humanised mouse models of acute graft-versus-host diseasebusulfanhPBMC
NETL
NSTL
维普
万方数据
