Effect and Mechanism of Cxcr4 Gene-Modified BMSC-Derived Exosomes on Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To explore the improvement effect of CXC chemokine receptor 4 (Cxcr4) gene-modified bone marrow mesenchymal stem cell (BMSC)-derived exosomes on aplastic anemia (AA), and make a preliminary exploration of the mechanism.@*METHODS@#Mouse BMSCs were isolated and cultured, then infected by recombinant lentivirus carrying Cxcr4 gene. The expression of green fluorescence was observed through fluorescence microscope, the expression of Cxcr4 mRNA was detected by real-time fluorescence quantitative PCR, and the BMSC-derived exosomes modified with Cxcr4 gene were extracted. Mouse models of AA were constructed, and control group, model group (AA), AA+BMSC group, AA+NC-BMSC group, AA+Cxcr4-BMSC group were set up. Except control group and model group, the other three groups of mice were injected 400 μl exosomes from different sources via the tail vein, after 2 weeks, the routine blood indices and the number of bone marrow nucleated cells were detected, the pathological changes of bone marrow were observed by HE staining, and the expression level of Treg cells was detected by flow cytometry.@*RESULTS@#Mouse BMSCs were successfully isolated, and BMSCs with high expression of Cxcr4 and their exosomes were obtained. Compared with the control group, the number of red blood cell (RBC), white blood cell (WBC), and platelet (PLT), the hemoglobin (Hb) content and proportion of Treg cells in the peripheral blood of mice in the model group significantly decreased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). The proliferation level of nucleated cells was low, and the medullary cavity was filled with a large number of fat cells. Compared with the model group, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+BMSC group, AA+NC-BMSC group, and AA+Cxcr4-BMSC group significantly increased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01), and pathological changes of bone marrow were improved. In addition, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+Cxcr4-BMSC group were significantly higher than those in the AA+BMSC group (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01).@*CONCLUSION@#Injection of Cxcr4 gene-modified BMSC-derived exosomes has a certain improvement effect on AA mice, and the mechanism may be related to an increase of the proportion of Treg cells.

Clinical Study on Calcitriol Combined with Sirolimus in the Treatment of Chronic Primary Immune Thrombocytopenia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical efficacy of calcitriol combined with sirolimus in the treatment of chronic primary immune thrombocytopenia (cITP) patients.@*METHODS@#A total of 146 adult cITP patients reated in the First Affiliated Hospital of Hebei North University from March 2017 to March 2020 were randomly divided into observation group (73 cases) and control group (73 cases) according to random number table. The control group was treated with oral sirolimus capsule, the observation group was treated with oral calcitriol capsule combined with sirolimus capsule, and the curative effect of the 2 groups was evaluated after continuous treatment for 6 weeks. The changes of World Health Organization (WHO) bleeding grade, laboratory related index, including peripheral blood regulatory T cell (Treg), serum 1,25-dihydroxy-vitamin D@*RESULTS@#The total effective rate of the observation group was 79.5% (58/73), which was significantly higher than 64.4% (47/73) of the control group (P<0.05). The revised WHO bleeding grades after treatment were significantly better than those before treatment in the 2 groups (P<0.05), but the observation group was improved more significantly than the control group (P<0.05). After treatment, platelet count (PLT), peripheral blood Treg cell ratio, and serum 1,25(OH)@*CONCLUSION@#The overall efficacy of calcitriol combined with sirolimus in the treatment of cITP in adults is satisfactory, which can effectively alleviate patient's condition, improve the quality of life, further increase the platelet level and decrease the expression of VDR in peripheral blood lymphocyte, the mechanism may be related to increasing the level of serum 1,25(OH)