Influence of methylprednisolone on cell component of donor graft and on H-2 haploidentical hematopoietic stem cell transplantation in mice / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the influence of methylprednisolone (MP) on cellular component in donor graft and on H-2 haploidentical hematopoietic stem cell transplantation (HSCT) in mice.</p><p><b>METHODS</b>A murine model of H-2 haploidentical HSCT was established by using of c57BL/6J male mouse as donor and (c57BL/6J x LB/C) F1 female mouse as recipient. The donor mouse received peripheral-blood (PB) progenitor cells mobilization regimens consisted of recombinant human granulocyte colony-stimulating factor (rhGCSF) alone (control group) or combined with MP in dose of 2 mg/kg daily [small-dose (SD) group], 10 mg/kg daily [middle-dose (MD) group], and 50 mg/kg daily [large-dose (LD) group] respectively. Percentage of T cell subsets, DC1 (HLA-DR+CD11c+) and CD34+ cell in the grafts were detected by flow cytometry. Transplant rejection,severity of GVHD and survival time were observed.</p><p><b>RESULTS</b>The percentages of CD3+ T cell in donor grafts in the three groups were significantly lower than that in control group (P < 0.05). The percentage of CD3+ CD4+ T cells decreased more significantly than that of CD3+ CD8+ T cells, and CD4/CD8 ratios decreased significantly. The percentage of CD4+ CD25+ T cells increased significantly, the percentage of DC1( HLA-DR+CD11c+) decreased and the percentage of CD34+ cells increased in all the three groups than in control group. There were significant differences in the percentage of CD3+ T cells, CD3+ CD4+ T cells and CD34+ cells in donor grafts among SD group, MD group and LD group (P < 0.05). The engraftment rates in control, SD, MD and LD groups were 90%, 100%, 100% and 80% respectively. Severity of aGVHD in each study group decreased significantly compared with that in control group (P < 0.05). There were statistical differences among different dosage groups (P < 0.05). Survival time after transplantation in all study groups were significantly longer than that in control group (P < 0.05), and in MD group was significantly longer than in SD group and LD groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Addition of methylprednisolone to routine donor mice HSC mobilization regimen has a definite effect in alleviating aGVHD and prolonging survival time of mouse after H-2 haploidentical HSCT. With a suitable dosage addition of methylprednisolone to donor mice HSC mobilization regimen could avoid the increasing risk of graft rejection.</p>