Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice

Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice
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DOI:
10.1016/s0168-8278(02)00043-0
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发表时间:
2002-05-01
影响因子:
25.7
通讯作者:
Yamaoka, Y
Yamaoka, Y
中科院分区:
医学1区
文献类型:
--
作者:
Fujii, H;Hirose, T;Yamaoka, Y

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背景/目标:本研究采用绿色荧光蛋白(GFP)转基因小鼠骨髓(BM)移植模型,观察部分肝切除术后骨髓细胞在肝再生过程中是否能分化为肝细胞。GFP阳性肝细胞的谱系标志物分析通过免疫染色和流式细胞术进行。DiI标记的乙酰化低密度脂蛋白的摄取或微球吞噬作用进行了检查在体外。骨髓和外周血(PB)细胞的谱系标志物的表达,和血管内皮生长因子(VEGF)在肝脏中的浓度也examined.Results:在肝切除小鼠,显着更多的GFP阳性细胞参与肝窦比假手术小鼠,表达CD 31,但不白蛋白。掺入乙酰化低密度脂蛋白但不掺入微球的细胞百分比为69.5 +/-3.4%,而两者均掺入的细胞百分比为28.3 +/- 2.6%,分别显示窦状内皮细胞和枯否细胞。还检测到GFP阳性肝细胞上CD 31和CD 16/CD 32的表达增加。肝再生过程中VEGF浓度的升高和肝脏,BM和PB细胞中的CD 34和Flk-1表达的增加表明内皮祖细胞mobilation.Conclusions:GFP细胞标记提供了直接证据的BM细胞参与肝切除术后,其中大多数是致力于肝窦内皮细胞可能通过内皮祖细胞动员的肝再生。(C)2002年欧洲肝脏研究协会。由Elsevier Science B. V.出版,版权所有。
Background/Aims: We examined whether bone marrow (BM) cells can commit to liver-consisting cells during liver regeneration after partial hepatectomy, using mice transplanted with green fluorescent protein (GFP) positive BM from GFP transgenic mice.Methods: Partial hepatectomy or sham operation was performed. Lineage marker analysis of GFP positive liver cells was by immunostaining and flow cytometry. DiI-labeled acetylated low-density lipoprotein uptake or microsphere phagocytosis was examined in vitro. Lineage marker expression in BM and peripheral blood (PB) cells, and the vascular endothelial growth factor (VEGF) concentration in the liver were also examined.Results: In hepatectomized mice, significantly more GFP positive cells participated in liver sinusoid than in sham-operated mice, expressing CD31 but not albumin. The percentage of cells that incorporated acetylated low-density lipoprotein but not microspheres was 69.5 +/- 3.4%, while 28.3 +/- 2.6% incorporated both, revealing sinusoidal endothelial and Kupffer cells, respectively. Increased expression of the CD31 and CD16/CD32 on GFP positive liver cells was also detected. The elevation of the VEGF concentration during liver regeneration and the increase in the CD34 and Flk-1 expression in the liver, BM, and PB cells suggested endothelial progenitor cell mobilization.Conclusions: GFP cell-marking provided direct evidence of the BM cells participation in liver regeneration after hepatectomy, where the majority was committed to sinusoidal endothelial cells probably through endothelial progenitor cell mobilization.(C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.