| ObjectiveTo analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia(SAA) after matched sibling donor (MSD) or haploidentical family donor (HFD)hematopoietic stem cell transplantation (HSCT) using the modified conditioning.MethodsThe clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively. The hematopoietic reconstitution, graft verus host disease (GVHD), transplantation related toxicity (TRT) and prognosis after transplantation were compared. Furthermore, the modifed conditioning included low-dose Cyclophosphamide (total dose 100 mg/kg) , infustion of third-party donor-derived mesenchymal stem cells.ResultsAll 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution.Among them, not only the recovery of neutrophils and platelets, but also the incidences of ?-? aGVHD, extensive cGVHD and TRT were not significantly different (the P value were 0.58, 0.61, 0.73, 0.73 and 0.67,respectively). After following-up for 32(2-66) months, 48 patients alive well,the one year overall survival were 86% in HFD-HSCT group and 89% in MSD-HSCT group, respectively ( P=0.58).Conclusions After Allo-HSCT using the modifed conditioning, patients with SAA achieved stable engraftment, low toxicity, mild GVHD and excellent outcomes.Furthermore, the HFD-HSCT achieved comparable outcomes to MSD-HSCT and may be served as an alternate therapy for patients with SAA.ObjectiveTo observe the influence of tacrolimus on the proliferative of umbilical cord mesenchymal stem cells(UC-MSC), and explore the mechanism and relationship of FK-506 accompany with UC-MSC therapy on the immunosuppression effect,which would provide evidence for prevention and treatment of GVHD.MethodsSurface antigens of UC-MSC were detected by flow Cytometry; The influence of tacrolimus on the proliferation of UC-MSC were detected by CCK8; The influence of tacrolimus on the apoptosis and cell Cycle of UC-MSC were detected by flow Cytometry; PHA-stimulated peripheral blood mononuclear cells were co-cultured with UC-MSC and/or different concentration of tacrolimus, the concentration of IFN-y in the medium was detected using ELISAResults1. Surface antigens that UC-MSC expressed include CD44, CD73, CD90, CD105 and CD29, while not CD11b, CD19, CD34, CD45, CD31 and HLA-DR.2. When UC-MSC were co-cultured with different concentration of tacrolimus for 24 and 48h, the proliferation of UC-MSC was decresed with the increased concentration of tacrolimus, but there was no statistical significance between experimental group and the control group.3. When UC-MSC were co-cultured with different concentration of tacrolimus for 48h, the apoptosis rate of UC-MSC was incresed with the increased concentration of tacrolimus, but there was no statistical significance between experimental group and the control group.4. When UC-MSC were co-cultured with different concentration of tacrolimus for 48h, the proportion of S phase UC-MSC was increased with the increased concentration of tacrolimus, and there was statistical significance between experimental group and the control group.5. When PHA-stimulated peripheral blood mononuclear cells were co-cultured with different concentration of tacrolimus for 48h, the concentration of IFN-y in the medium was decreased with the increased concentration of tacrolimus, and there was statistical significance between experimental group and the control group.6. When UC-MSC were co-cultured with different proportion of PHA-stimulated peripheral blood mononuclear cells for 72h, the concentration of IFN-y in the medium was decreased with the increased concentration of tacrolimus, and there was statistical significance between experimental group and the control group.7. When PHA-stimulated peripheral blood mononuclear cells were co-cultured with the FK-506, UC-MSC and FK-506+UC-MSC for 72h, the secretion of IFN-y in UC-MSC group was higher than FK-506+UC-MSC group,while it was lower than FK-506 group, and there was statistical significance between experimental group and the control group.ConclusionsThere was no inhibiting effect of on UC-MSC, but tacrolimus can convert the G0/G1 phase UC-MSC cells to tacrolimus S phase, that is to say, tacrolimus could promote division of UC-MSC. The IFN-y secretion of PHA-stimulated peripheral blood mononuclear cells can be suppressed by UC-MSC and tacrolimus, which implied both UC-MSC and tacrolimus had immunosuppressive action on the T-lymphoCytes. UC-MSC and tacrolimus had immunosuppression synergistic effect.which would provide evidence for prevention and treatment of GVHD. |
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