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基于干细胞的肝脏再生机遇:现状与展望

Stem cell-based regenerative opportunities for the liver: State of the art and beyond.

作者信息

Tsolaki Eleftheria, Yannaki Evangelia

机构信息

Eleftheria Tsolaki, Evangelia Yannaki, Gene and Cell Therapy Center, Hematology Department-BMT Unit, George Papanicolaou Hospital, 57010 Thessaloniki, Greece.

出版信息

World J Gastroenterol. 2015 Nov 21;21(43):12334-50. doi: 10.3748/wjg.v21.i43.12334.

DOI:10.3748/wjg.v21.i43.12334
PMID:26604641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4649117/
Abstract

The existing mismatch between the great demand for liver transplants and the number of available donor organs highlights the urgent need for alternative therapeutic strategies in patients with acute or chronic liver failure. The rapidly growing knowledge on stem cell biology and the intrinsic repair processes of the liver has opened new avenues for using stem cells as a cell therapy platform in regenerative medicine for hepatic diseases. An impressive number of cell types have been investigated as sources of liver regeneration: adult and fetal liver hepatocytes, intrahepatic stem cell populations, annex stem cells, adult bone marrow-derived hematopoietic stem cells, endothelial progenitor cells, mesenchymal stromal cells, embryonic stem cells, and induced pluripotent stem cells. All these highly different cell types, used either as cell suspensions or, in combination with biomaterials as implantable liver tissue constructs, have generated great promise for liver regeneration. However, fundamental questions still need to be addressed and critical hurdles to be overcome before liver cell therapy emerges. In this review, we summarize the state-of-the-art in the field of stem cell-based therapies for the liver along with existing challenges and future perspectives towards a successful liver cell therapy that will ultimately deliver its demanding goals.

摘要

肝移植的巨大需求与可用供体器官数量之间现有的不匹配凸显了急性或慢性肝衰竭患者对替代治疗策略的迫切需求。干细胞生物学以及肝脏内在修复过程方面迅速增长的知识为在再生医学中使用干细胞作为肝病细胞治疗平台开辟了新途径。作为肝脏再生来源,已有大量细胞类型被研究:成体和胎儿肝脏肝细胞、肝内干细胞群体、肝门干细胞、成体骨髓来源的造血干细胞、内皮祖细胞、间充质基质细胞、胚胎干细胞和诱导多能干细胞。所有这些高度不同的细胞类型,无论是作为细胞悬液使用,还是与生物材料结合用作可植入肝脏组织构建体,都为肝脏再生带来了巨大希望。然而,在肝细胞治疗出现之前,仍需解决一些基本问题并克服关键障碍。在本综述中,我们总结了基于干细胞的肝脏治疗领域的最新进展以及现有挑战和未来展望,以期实现最终能达成其苛刻目标的成功肝细胞治疗。

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本文引用的文献

1
Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis.在严重急性暴发性肝炎动物模型中研究了未分化间充质基质细胞和脂肪组织作为肝脏再生治疗来源的有用特性。
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Recent advances in 3D printing of biomaterials.生物材料 3D 打印的最新进展。
J Biol Eng. 2015 Mar 1;9:4. doi: 10.1186/s13036-015-0001-4. eCollection 2015.
3
Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice.HGF 和 FGF4 预处理的间充质干细胞可减少小鼠肝纤维化。
Stem Cells Int. 2015;2015:747245. doi: 10.1155/2015/747245. Epub 2015 Jan 20.
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Adipose-derived mesenchymal stem cells inhibit activation of hepatic stellate cells in vitro and ameliorate rat liver fibrosis in vivo.脂肪来源的间充质干细胞在体外抑制肝星状细胞的活化,并在体内改善大鼠肝纤维化。
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Enhanced antioxidant capacity of dental pulp-derived iPSC-differentiated hepatocytes and liver regeneration by injectable HGF-releasing hydrogel in fulminant hepatic failure.牙髓来源的诱导多能干细胞分化的肝细胞抗氧化能力增强以及可注射的释放肝细胞生长因子的水凝胶在暴发性肝衰竭中促进肝脏再生
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Human bone marrow mesenchymal stem cell-derived hepatocytes express tissue inhibitor of metalloproteinases 4 and follistatin.人骨髓间充质干细胞源性肝细胞表达金属蛋白酶组织抑制剂4和卵泡抑素。
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A case of granulocyte-colony stimulating factor/plasmapheresis-induced activation of granulocyte-colony stimulating factor-positive hepatic progenitors in acute-on-chronic liver failure.1例慢性肝衰竭急性发作患者中粒细胞集落刺激因子/血浆置换诱导粒细胞集落刺激因子阳性肝祖细胞激活的病例
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Basic fibroblast growth factor-treated adipose tissue-derived mesenchymal stem cell infusion to ameliorate liver cirrhosis via paracrine hepatocyte growth factor.碱性成纤维细胞生长因子处理的脂肪组织来源间充质干细胞输注通过旁分泌肝细胞生长因子改善肝硬化
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