胡锴勋,赵士富,郭梅,等.间充质干细胞促进半相合骨髓移植治疗急性放射病小鼠的实验研究[J].中华放射医学与防护杂志,2008,28(2):135-138.HU Kai-xun,ZHAO Shi-fu,GUO Mei,et al.Experimental study of MSCs promoting haploid hematopoietic stem cell transplantation in treatment for mice with acute radiation syndrome[J].Chin J Radiol Med Prot,2008,28(2):135-138 |
间充质干细胞促进半相合骨髓移植治疗急性放射病小鼠的实验研究 |
Experimental study of MSCs promoting haploid hematopoietic stem cell transplantation in treatment for mice with acute radiation syndrome |
投稿时间:2007-04-27 |
DOI: |
中文关键词: 急性放射病 骨髓间充质干细胞 造血干细胞移植 多脏器衰竭 |
英文关键词:Acute radiation syndrome Mesenchymal stem cells Multiple organ failure SCT |
基金项目:国家“863”基金资助项目(2002AA216081) |
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中文摘要: |
目的 探讨骨髓间充质干细胞(MSCs)促进半相合造血干细胞移植(haploid-SCT)治疗急性放射病小鼠的作用及机制。方法 60Co γ射线照射BALB/C(H-2d)雌性小鼠8Gy,单独输注半相合CB6F1(H-2
bd) 雄性小鼠骨髓细胞1×109/kg(I组),或联合CB6F1 雌性小鼠MSCs不同数量级1.5×108/kg (a组)、5×107/kg (b组)和2.5×107/kg (c组)治疗,比较放射病小鼠的生存分析。同时,MSCs组小鼠尾静脉输注经cm-DiI膜染剂标记的CB6F1雌性小鼠MSCs和CB6F1雄性小鼠的骨髓细胞,与只输注CB6F1骨髓细胞的对照组比较,观察移植后不同时间供者细胞在受者骨髓的植入率、供者MSCs在受者体内发布、外周血象、T淋巴细胞亚群、胸骨骨髓病理和慢性移植物抗宿主病(GVHD)发生情况。结果 a组小鼠早期死亡率增加;b和c组存活率高于I组(P<0.05),但二组之间差异无统计学意义。移植后30 d,MSCs组受者骨髓的sry基因高于对照组。移植后MSCs主要集中在胸腺、骨髓、肝和小肠中,有形态改变。MSCs组的白细胞、血小板恢复较快。照射后15和30 d,MSCs组小鼠骨髓腔中的巨核细胞明显高于对照组。移植后7、14和30 d,MSCs组CD3高于对照组(P<0.05);移植后14和30 d,MSCs组CD4阳性细胞率和CD4/CD8值高于对照组(P<0.05)。MSC组慢性GVHD症状出现较对照组晚30 d。结论 MSCs通过促进干细胞植入,改善造血微环境,促进造血恢复,加快T淋巴细胞的恢复,延缓GVHD的发生时间和促进放射损伤的组织器官的修复,加强了半相合骨髓移植对急性放射病的治疗作用。 |
英文摘要: |
Objective To investigate the mechanism of mesenchymal stem cells in enhancing the effects of haploid matched bone marrow cells transplantation in mice with acute radiation syndrome (ARS).Methods The survival of mice infused with different levels of MSCs and bone marrow cells after 8 Gy TBI were examined. BALB/c female mice irradiated with 8 Gy of 60Coγ-rays were randomly divided into two groups, MSCs group, infused with MSCs of female CB6F1 mice labeled with cm-DiI and bone marrow monocytes of male CB6F1,Control group, only infused with bone marrow monocytes. Peripheral blood counts, T-lymphocyte subpopulation of peripheral blood cells, the sry-gene chimerism of bone marrow of the receiptors, the distribution of MSCs in the receiptors, the occurrence time of cGVHD, pathologic variety of medulla were observed. ResultsMSCs improved the survival of mice after 8 TBI, but 1.5×108/kg of MSCs increased the mortality of irradiated mice. In comparison with the control group, leukocytes and plastocytes recovered rapidly in MSCs group. Megacaryocytes in sternum marrows grew fastly in MSC group. The percent of CD3 and CD4 positive cells in the MSCs group were higher than those in control post-transplantation. The sry-gene chimerism of bone marrow of the receiptors was higher in the MSCs group than that in the control at 30 d. The MSCs were distributed in intestine, thymus, bone marrow, liver, heart of the receiptors at 30 d. The cGVHD occurrence was 30 d later in MSCs group than that of the control. Conclusions MSCs could improve stem cell engraftment, enhance T-lymphocyte and plastocytes recovery, delay occurrence of cGVHD, repair injured organs and increase survivals. It is indicated that MSCs can enhance the treatment effects of haploid hematopoietic stem cells transplant for ARS. |
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