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肝脏疾病的细胞治疗:过去、现在与未来。

Cell therapy for liver disorders: past, present and future.

作者信息

Ortuño-Costela M Carmen, Pinzani Massimo, Vallier Ludovic

机构信息

Berlin Institute of Health, BIH Centre for Regenerative Therapies, Charité-Universitätsmedizin, Berlin, Germany.

Max Planck Institute for Molecular Genetics, Berlin, Germany.

出版信息

Nat Rev Gastroenterol Hepatol. 2025 May;22(5):329-342. doi: 10.1038/s41575-025-01050-2. Epub 2025 Mar 18.


DOI:10.1038/s41575-025-01050-2
PMID:40102584
Abstract

The liver fulfils a plethora of vital functions and, due to their importance, liver dysfunction has life-threatening consequences. Liver disorders currently account for more than two million deaths annually worldwide and can be classified broadly into three groups, considering their onset and aetiology, as acute liver diseases, inherited metabolic disorders and chronic liver diseases. In the most advanced and severe forms leading to liver failure, liver transplantation is the only treatment available, which has many associated drawbacks, including a shortage of organ donors. Cell therapy via fully mature cell transplantation is an advantageous alternative that may be able to restore a damaged organ's functionality or serve as a bridge until regeneration can occur. Pioneering work has shown that transplanting adult hepatocytes can support liver recovery. However, primary hepatocytes cannot be grown extensively in vitro as they rapidly lose their metabolic activity. Therefore, different cell sources are currently being tested as alternatives to primary cells. Human pluripotent stem cell-derived cells, chemically induced liver progenitors, or 'liver' organoids, hold great promise for developing new cell therapies for acute and chronic liver diseases. This Review focuses on the advantages and drawbacks of distinct cell sources and the relative strategies to address different therapeutic needs in distinct liver diseases.

摘要

肝脏具有众多重要功能,因其重要性,肝功能障碍会带来危及生命的后果。目前,肝脏疾病在全球每年导致超过200万人死亡,根据发病情况和病因,大致可分为三类,即急性肝病、遗传性代谢紊乱和慢性肝病。在导致肝衰竭的最晚期和最严重形式中,肝移植是唯一可用的治疗方法,但它有许多相关缺点,包括器官供体短缺。通过完全成熟细胞移植进行的细胞治疗是一种有利的替代方法,可能能够恢复受损器官的功能,或在再生发生之前起到桥梁作用。开创性工作表明,移植成人肝细胞可支持肝脏恢复。然而,原代肝细胞在体外不能大量培养,因为它们会迅速丧失代谢活性。因此,目前正在测试不同的细胞来源作为原代细胞的替代物。人多能干细胞衍生的细胞、化学诱导的肝祖细胞或“肝脏”类器官,在开发针对急性和慢性肝病的新细胞疗法方面具有巨大潜力。本综述重点关注不同细胞来源的优缺点,以及针对不同肝病满足不同治疗需求的相关策略。

相似文献

[1]
Cell therapy for liver disorders: past, present and future.

Nat Rev Gastroenterol Hepatol. 2025-5

[2]
Present and Future Perspectives of Using Human-Induced Pluripotent Stem Cells and Organoid Against Liver Failure.

Cell Transplant. 2019-12-16

[3]
Concise review: cell therapies for hereditary metabolic liver diseases-concepts, clinical results, and future developments.

Stem Cells. 2015-4

[4]
Cell-based liver therapies: past, present and future.

Philos Trans R Soc Lond B Biol Sci. 2018-7-5

[5]
Cell therapy in chronic liver disease.

Curr Opin Gastroenterol. 2016-5

[6]
Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration.

Cells. 2020-2-12

[7]
Clinical Application of Pluripotent Stem Cells: An Alternative Cell-Based Therapy for Treating Liver Diseases?

Transplantation. 2016-12

[8]
Human pluripotent stem cells for modelling human liver diseases and cell therapy.

Curr Gene Ther. 2013-4

[9]
The Use of Induced Pluripotent Stem Cells for the Study and Treatment of Liver Diseases.

Curr Protoc Toxicol. 2016-2-1

[10]
Current status of hepatocyte-like cell therapy from stem cells.

Surg Today. 2021-3

引用本文的文献

[1]
Recapitulating dengue virus infection with human pluripotent stem cell-derived liver organoids for antiviral screening.

Nat Commun. 2025-8-28

[2]
Fisetin Attenuates Zinc Overload-Induced Hepatotoxicity in Mice via Autophagy-Dependent Nrf2 Activation.

Int J Mol Sci. 2025-5-22

本文引用的文献

[1]
Pancreatic islet transplantation: current advances and challenges.

Front Immunol. 2024

[2]
Acquisition of epithelial plasticity in human chronic liver disease.

Nature. 2024-6

[3]
Efficient expansion and CRISPR-Cas9-mediated gene correction of patient-derived hepatocytes for treatment of inherited liver diseases.

Cell Stem Cell. 2024-8-1

[4]
Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth.

Nat Commun. 2024-5-13

[5]
Cholangiocyte Organoids: The New Frontier in Regenerative Medicine for the Study and Treatment of Cholangiopathies.

J Clin Med. 2024-3-21

[6]
Cryopreserved cGMP-compliant human pluripotent stem cell-derived hepatic progenitors rescue mice from acute liver failure through rapid paracrine effects on liver cells.

Stem Cell Res Ther. 2024-3-12

[7]
Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure.

Cell Stem Cell. 2024-4-4

[8]
Hepatic organoids move from adolescence to maturity.

Liver Int. 2024-6

[9]
Macrophage cytotherapy on liver cirrhosis.

Front Pharmacol. 2023-12-15

[10]
Cell-therapy for Parkinson's disease: a systematic review and meta-analysis.

J Transl Med. 2023-9-7

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