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骨髓细胞增强小鼠肝大部切除术后的肝再生。

Bone marrow cells enhance liver regeneration after massive hepatectomy in mice.

机构信息

Department of Surgery, Hirakata Hospital, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, Osaka, 573-1191, Japan,

出版信息

Dig Dis Sci. 2014 Jul;59(7):1484-9. doi: 10.1007/s10620-014-3032-7. Epub 2014 Jan 23.

DOI:10.1007/s10620-014-3032-7
PMID:24452841
Abstract

BACKGROUND

Recent evidence indicates that transplanted autologous bone marrow cells (BMCs) can be converted into functional liver cells. BMC therapy can improve hepatic function and increase the potential for liver regeneration in patients with serious liver damage. We investigated whether BMC therapy influenced liver regeneration after massive hepatectomy in mice.

METHODS

Male C57/BL6 mice underwent 70 % hepatectomy, followed by injection of BMCs via the portal vein (PV group), BMCs via the tail vein (IV group), or saline via the portal vein (control group). Analysis of serum enzyme levels and liver histology was performed on postoperative days (POD) 1, 3, and 5.

RESULTS

Compared with the control group, the rate of liver regeneration on POD 3 and 5 was significantly higher in the PV group, but not in the IV group. Examination of the mitotic index and Ki-67 labeling index revealed that the increased liver regeneration resulted from stimulation of DNA synthesis. On POD 3, the serum levels of interleukin (IL)-6 and hepatocyte growth factor (HGF) were significantly higher and the expression of IL-6 and HGF mRNA in the remnant liver tended to be higher in the PV group than in the control group. Histological examination showed BMCs in the liver of the PV group, as well as conversion of BMCs into liver cells.

CONCLUSIONS

Our findings indicate that the injection of BMCs via the portal vein, but not the injection of BMCs via the tail, enhances liver regeneration after massive hepatectomy in mice.

摘要

背景

最近的证据表明,移植的自体骨髓细胞(BMC)可以转化为功能性肝细胞。BMC 治疗可以改善肝功能,增加严重肝损伤患者的肝脏再生潜力。我们研究了 BMC 治疗是否会影响小鼠肝大部切除术后的肝脏再生。

方法

雄性 C57/BL6 小鼠行 70%肝切除术,随后经门静脉(PV 组)、尾静脉(IV 组)注射 BMC 或经门静脉注射生理盐水(对照组)。术后第 1、3、5 天检测血清酶水平和肝组织学。

结果

与对照组相比,PV 组术后第 3、5 天肝再生率明显升高,但 IV 组无此变化。通过有丝分裂指数和 Ki-67 标记指数检查发现,肝再生增加是由于 DNA 合成的刺激。在术后第 3 天,PV 组血清白细胞介素(IL)-6 和肝细胞生长因子(HGF)水平明显升高,残肝中 IL-6 和 HGF mRNA 的表达也趋于升高。组织学检查显示,PV 组的 BMC 存在于肝脏中,并且 BMC 转化为肝细胞。

结论

我们的研究结果表明,经门静脉注射 BMC 而非尾静脉注射 BMC 可增强小鼠肝大部切除术后的肝再生。

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本文引用的文献

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Stimulation of liver regeneration after hepatectomy in mice by injection of bone marrow mesenchymal stem cells via the portal vein.通过门静脉注射骨髓间充质干细胞刺激小鼠肝切除术后的肝再生。
Transplant Proc. 2012 May;44(4):1107-9. doi: 10.1016/j.transproceed.2012.01.088.
2
Practical barriers to delivering autologous bone marrow stem cell therapy as an adjunct to liver resection.作为肝切除的辅助治疗,自体骨髓干细胞治疗的实际障碍。
Stem Cells Dev. 2010 Feb;19(2):155-62. doi: 10.1089/scd.2009.0412.
3
The BALANCE Study: clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction.
BALANCE研究:急性心肌梗死患者冠状动脉内自体骨髓细胞移植后的临床益处及长期预后
J Am Coll Cardiol. 2009 Jun 16;53(24):2262-9. doi: 10.1016/j.jacc.2009.02.051.
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The use of stem cells in liver disease.干细胞在肝脏疾病中的应用。
Curr Opin Organ Transplant. 2009 Feb;14(1):64-71. doi: 10.1097/MOT.0b013e328320fd7b.
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Current status of autologous bone marrow cell infusion therapy for liver cirrhosis patients.肝硬化患者自体骨髓细胞输注治疗的现状。
Hepatol Res. 2008 Nov;38 Suppl 1:S72-5. doi: 10.1111/j.1872-034X.2008.00430.x.
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HA/GSA-Rmax ratio as a predictor of postoperative liver failure.HA/GSA-Rmax比值作为术后肝衰竭的预测指标。
World J Surg. 2008 Nov;32(11):2410-8. doi: 10.1007/s00268-008-9725-3.
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Critical review of clinical trials of bone marrow stem cells in liver disease.对肝脏疾病中骨髓干细胞临床试验的批判性综述。
Gastroenterology. 2008 Aug;135(2):438-50. doi: 10.1053/j.gastro.2008.05.040. Epub 2008 May 15.
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Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis.失代偿期肝硬化患者自体骨髓间充质干细胞移植的1期试验
Arch Iran Med. 2007 Oct;10(4):459-66.
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Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration.自体CD133+骨髓细胞经门静脉应用于肝脏:支持肝再生的新概念。
Stem Cells. 2005 Apr;23(4):463-70. doi: 10.1634/stemcells.2004-0283.