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干细胞在肝脏疾病中的应用。

The use of stem cells in liver disease.

作者信息

Flohr Tanya R, Bonatti Hugo, Brayman Kenneth L, Pruett Timothy L

机构信息

Department of Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.

出版信息

Curr Opin Organ Transplant. 2009 Feb;14(1):64-71. doi: 10.1097/MOT.0b013e328320fd7b.

DOI:10.1097/MOT.0b013e328320fd7b
PMID:19337149
Abstract

PURPOSE OF REVIEW

Cell transplantation to restore liver function as an alternative to whole liver transplantation has thus far not been successful in humans.

RECENT FINDINGS

Adult mature hepatocytes and various populations of liver progenitors and stem cells are being studied for their regenerative capabilities. Hepatocyte transplantation to treat metabolic deficiencies has shown promising early improvement in liver function; however, long-term success has not been achieved. Liver progenitor cells can now be identified and were shown to be capable to differentiate into a hepatocyte-like phenotype. Despite evidence of mesenchymal stem cell fusion in animal models of liver regeneration, encouraging results were seen in a small group of patients receiving autologous transplantation of CD133 mesenchymal stem cells to repopulate the liver after extensive hepatectomy for liver masses. Ethical issues, availability, potential rejection and limited understanding of the totipotent capabilities of embryonic stem cells are the limitations that prevent their use for restoration of liver function. The effectiveness of embryonic stem cells to support liver function has been proven with their application in the bioartificial liver model in rodents.

SUMMARY

There is ongoing research to restore liver function in cell biology, animal models and clinical trials using mature hepatocytes, liver progenitor cells, mesenchymal stem cells and embryonic stem cells.

摘要

综述目的

细胞移植作为全肝移植的替代方法来恢复肝功能,目前在人类中尚未取得成功。

最新发现

正在研究成年成熟肝细胞以及各种肝祖细胞和干细胞群体的再生能力。肝细胞移植治疗代谢缺陷已显示出早期肝功能有令人鼓舞的改善;然而,尚未取得长期成功。现在可以识别肝祖细胞,并且已证明它们能够分化为肝细胞样表型。尽管在肝再生动物模型中有间充质干细胞融合的证据,但在一小部分接受CD133间充质干细胞自体移植以在因肝肿块进行广泛肝切除术后重建肝脏的患者中看到了令人鼓舞的结果。伦理问题、可用性、潜在排斥以及对胚胎干细胞全能能力的了解有限是阻碍其用于恢复肝功能的限制因素。胚胎干细胞在啮齿动物生物人工肝模型中的应用已证明其支持肝功能的有效性。

总结

目前正在进行利用成熟肝细胞、肝祖细胞、间充质干细胞和胚胎干细胞在细胞生物学、动物模型和临床试验中恢复肝功能的研究。

相似文献

1
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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Progress and future challenges in stem cell-derived liver technologies.干细胞衍生肝脏技术的进展与未来挑战
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Hepatocyte transplantation: waiting for stem cells.肝细胞移植:等待干细胞
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From hepatocytes to stem and progenitor cells for liver regenerative medicine: advances and clinical perspectives.从肝细胞到肝再生医学的干细胞和祖细胞:进展和临床展望。
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Pluripotent Stem Cell-derived Strategies to Treat Acute Liver Failure: Current Status and Future Directions.多能干细胞衍生的治疗急性肝衰竭策略:现状与未来方向。
J Clin Transl Hepatol. 2022 Aug 28;10(4):692-699. doi: 10.14218/JCTH.2021.00353. Epub 2022 Mar 9.
2
Inhibition of the RhoGTPase Cdc42 by ML141 enhances hepatocyte differentiation from human adipose-derived mesenchymal stem cells via the Wnt5a/PI3K/miR-122 pathway: impact of the age of the donor.ML141 通过 Wnt5a/PI3K/miR-122 通路抑制 RhoGTPase Cdc42 增强人脂肪间充质干细胞向肝细胞的分化:供体年龄的影响。
Stem Cell Res Ther. 2018 Jun 19;9(1):167. doi: 10.1186/s13287-018-0910-5.
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Model systems and clinical applications of hepatic stem cells for liver regeneration.
用于肝脏再生的肝干细胞的模型系统与临床应用
Hepatol Int. 2012 Jun;6(3):564-75. doi: 10.1007/s12072-011-9323-6. Epub 2011 Dec 21.
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Novel management of acute or secondary biliary liver conditions using hepatically differentiated human dental pulp cells.使用肝分化的人牙髓细胞对急性或继发性胆汁性肝病进行新型管理。
Tissue Eng Part A. 2015 Feb;21(3-4):586-93. doi: 10.1089/ten.TEA.2014.0162. Epub 2014 Nov 7.
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Bone mesenchymal stem cell transplantation via four routes for the treatment of acute liver failure in rats.通过四种途径进行骨间充质干细胞移植治疗大鼠急性肝衰竭
Int J Mol Med. 2014 Oct;34(4):987-96. doi: 10.3892/ijmm.2014.1890. Epub 2014 Aug 11.
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Bone marrow cells enhance liver regeneration after massive hepatectomy in mice.骨髓细胞增强小鼠肝大部切除术后的肝再生。
Dig Dis Sci. 2014 Jul;59(7):1484-9. doi: 10.1007/s10620-014-3032-7. Epub 2014 Jan 23.
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Human adipose tissue derived stem cells promote liver regeneration in a rat model of toxic injury.人脂肪组织来源的干细胞促进毒损伤大鼠模型的肝再生。
Stem Cells Int. 2013;2013:534263. doi: 10.1155/2013/534263. Epub 2013 Nov 7.
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Unbalanced distribution of materials: the art of giving rise to hepatocytes from liver stem/progenitor cells.物质的不平衡分布:从肝干细胞/祖细胞中产生肝细胞的艺术。
J Cell Mol Med. 2014 Jan;18(1):1-14. doi: 10.1111/jcmm.12183. Epub 2013 Nov 28.
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Stages based molecular mechanisms for generating cholangiocytes from liver stem/progenitor cells.基于阶段的分子机制,用于从肝干细胞/祖细胞中生成胆管细胞。
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