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纸质出版:2011
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李长珠,梁光萍,汤旭东,吴玉云,汪苏敏,赵晶京,房殿春,杨仕明.骨髓来源细胞参与肝脏损伤的修复[J].陆军军医大学学报(原第三军医大学学报),2011,33(09):887-891.
Li Changzhu,Liang Guangping,Tang Xudong,Wu Yuyun,Wang Sumin,Zhao Jingjing,Fang Dianchun,Yang Shiming.Bone marrow stem cells are involved in liver repair in mice[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(09):887-891.
李长珠,梁光萍,汤旭东,吴玉云,汪苏敏,赵晶京,房殿春,杨仕明.骨髓来源细胞参与肝脏损伤的修复[J].陆军军医大学学报(原第三军医大学学报),2011,33(09):887-891. DOI:
Li Changzhu,Liang Guangping,Tang Xudong,Wu Yuyun,Wang Sumin,Zhao Jingjing,Fang Dianchun,Yang Shiming.Bone marrow stem cells are involved in liver repair in mice[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(09):887-891. DOI:
目的 探讨小鼠骨髓来源干细胞(bone marrow stem cells
BMSCs)在体内分化为肝细胞的可行性及BMSCs是否参与肝功能受损的修复。 方法 30只雌性C57BL/6小鼠全身一次性接受10 Gy
60
Co射线照射后,立即接受同品系雄性小鼠骨髓干细胞移植。移植后21 d后以CCl
4
致骨髓嵌合小鼠肝功能受损,并于CCl
4
致伤后第2、3、4、7、14、21、28天取骨髓嵌合小鼠肝脏,冰冻切片行Y染色体FISH和白蛋白(albumin,ALB)免疫荧光双标染色法,检测BMSC阳性细胞在受体小鼠肝内的分化情况,ELISA法检测肝脏基质细胞衍生因子-1(stromal cell-derived factor1,SDF-1)及其趋化因子受体(CXCR-4)、肝细胞生长因子(hepatocyte growth factor,HGF)、干细胞因子(stem cell factor,SCF)的表达。 结果 伤后2、3、4、7、14、21、28 d骨髓嵌合小鼠肝内皆可见FISH和ALB共表达的双阳性细胞,计数Y染色体FISH与ALB双阳性的细胞数量为3.763%~5.578%。ELISA法检测相关干细胞因子发现,在肝损伤后同一批次各时相点肝脏组织匀浆标本中SDF-1、CXCR-4、SCF、HGF 4种因子均呈现增高趋势,并在肝损伤第21天达到高峰表现,与其他时相点相比显著增加(P0.05),同FISH与ALB荧光双标记共表达计数结果一致。 结论 BMSCs可通过直接分化为肝细胞及分泌相关细胞因子间接促进受体肝脏干细胞增殖参与受损肝脏的修复。
Objective To investigate the feasibility of bone marrow derived stem cells (bone marrow stem cells
BMSCs) differentiate into hepatocytes in vivo
in order to provide the theoretical basis for BMSCs participating in the repair of injuring liver. Methods After 30 female C57BL/6 mice received a whole body radiation of 10 Gy
60
Co
they were given bone marrow transplantation
from the same strain male mice immediately. In 21 d after transplantation
these female mice received an intraperitoneal injection of carbon tetrachloride (CCl
4
) to induce liver injury. Then their livers were removed for double fluorescence labeling of Y chromosome by FISH and albumin (ALB) by immunofluorescence at the 2nd
3rd
4th
7th
14th
21st and 28th d after CCl
4
injection
which will indicate whether the BMSCs were differentiated to hepatocytes. Meanwhile
the liver content of several associated factors
such as stromal cell-derived factor1 (SDF-1) and its receptor CXCR-4
hepatocyte growth factor (HGF) and stem cell factor (SCF) were also detected by ELISA. Results Double positive cells
which co-expressed Y chromosome by FISH and Alb by immunofluorescence
were found from 2 to 28 d after after CCl
4
injury at a positive rate of 3.763% to 5.578%. Meanwhile
ELISA indicated that the liver contents of SDF-1
CXCR-4
SCF and HGF were increased gradually after injury with CCl
4
and reached the peak at the 21st day after CCl
4
injury (P0.05
compared with those at other time points)
which was consistent with the counting of double positive cells by FISH and immunofluorescence. Conclusion BMSCs may directly differentiate to live cells in vivo and/or indirectly promote original liver stem cells proliferation and differentiation by secreting cellular factors
and thus be involved in the repair of injuring liver. These results provide the evidence for BMSCs in the treatment of end stage liver disease.
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