基因修饰间充质干细胞在肝脏疾病治疗中的应用价值

赵婷婷; 李俊峰; 周丹; 高晓琴; 岳伟; 王汝琴; 张立婷

doi:10.12449/JCH250633

基因修饰间充质干细胞在肝脏疾病治疗中的应用价值

DOI: 10.12449/JCH250633

赵婷婷¹,
李俊峰^{1, 2a},
周丹^2a,
高晓琴^2a,
岳伟^2b,
王汝琴^2a,
张立婷^{1, 2a, 2c, , ,}

1.
兰州大学第一临床医学院，兰州 730000
2a.
兰州大学第一医院肝病科 & 传染病研究室，兰州 730000
2b.
兰州大学第一医院感染科，兰州 730000
2c.
兰州大学第一医院门静脉高压研究所（中心），兰州 730000

基金项目:

国家自然科学基金 (82360132);

甘肃省卫生健康行业科技创新重大项目 (GSWSZD2024-11);

甘肃省重点研发计划项目 (22YF7FA085);

甘肃省联合科研基金项目 (23JRRA1489);

甘肃省联合科研基金项目 (24JRRA911);

甘肃省中医药课题重点项目 (GZKZ-2022-7);

甘肃省重点人才项目 (Gan Group No. ［2024］4)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：赵婷婷负责查阅文献，撰写文章；周丹、高晓琴、岳伟、王汝琴负责审校；李俊峰、张立婷负责指导立题，文章修改。

详细信息

通信作者:
张立婷， zlt08@qq.com （ORCID： 0009-0005-1259-5747）

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出版历程
- 收稿日期: 2024-09-25
- 录用日期: 2024-12-04
- 出版日期: 2025-06-25

Application value of gene-modified mesenchymal stem cells in liver diseases

Tingting ZHAO¹,
Junfeng LI^{1, 2a},
Dan ZHOU^2a,
Xiaoqin GAO^2a,
Wei YUE^2b,
Ruqin WANG^2a,
Liting ZHANG^{1, 2a, 2c
, ,
,}

1.
The First Clinical Medical College of Lanzhou University，Lanzhou 730000，China
2a.
Department of Hepatology & Infectious Diseases，The First Hospital of Lanzhou University，Lanzhou 730000，China
2b.
Department of Infectious Diseases，The First Hospital of Lanzhou University，Lanzhou 730000，China
2c.
Institute of Portal Hypertension，The First Hospital of Lanzhou University，Lanzhou 730000，China

Research funding:

National Natural Science Foundation of China (82360132);

Major Project of Science and Technology Innovation in Health Sector of Gansu Province (GSWSZD2024-11);

Key R & D Program of Gansu Province (22YF7FA085);

Joint Research Fund Project of Gansu Province (23JRRA1489);

Joint Research Fund Project of Gansu Province (24JRRA911);

Key Project of Traditional Chinese Medicine in Gansu Province (GZKZ-2022-7);

Gansu Provincial Key Talent Project (Gan Group No. ［2024］4)

More Information

Corresponding author: ZHANG Liting， zlt08@qq.com （ORCID： 0009-0005-1259-5747）

摘要

摘要: 间充质干细胞的免疫调节、修复和促再生功能使其成为肝脏疾病的潜在治疗方法之一。目前，已经开发出病毒和非病毒递送方法对间充质干细胞进行基因修饰，基因修饰可以促进间充质干细胞存活、归巢、分泌细胞因子等特性，增强间充质干细胞治疗肝脏疾病的能力。本文主要概述基因修饰间充质干细胞治疗肝脏疾病的研究进展，以期为肝脏疾病的临床治疗提供新的见解和策略。
- 间质干细胞 /
- 生物，基因修饰 /
- 肝疾病 /
- 治疗学
Abstract: The immunomodulatory， repair， and regeneration-promoting functions of mesenchymal stem cells make them one of the potential treatment methods for liver diseases. At present， viral and non-viral delivery methods have been developed to genetically modify mesenchymal stem cells， and gene modification can promote the survival， homing， and cytokine secretion of mesenchymal stem cells， thereby enhancing the ability of mesenchymal stem cells to treat liver diseases. This article mainly summarizes the research advances in gene-modified mesenchymal stem cells in the treatment of liver diseases， in order to provide new insights and strategies for the clinical treatment of liver diseases.
- Mesenchymal Stem Cells /
- Organisms， Genetically Modified /
- Liver Disease /
- Therapeutics

HTML全文

注： Q-HSC，静止型HSC；A-HSC，激活态HSC；RPL-1，再生肝磷酸酶-1。

图 1 基因修饰的MSC在肝脏疾病治疗中的应用价值

Figure 1. The application value of gene-modified mesenchymal stem cells in liver diseases

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表 1 基因修饰的MSC在肝病中的应用

Table 1. Application of gene-modified mesenchymal stem cells in liver diseases

干细胞	基因	基因编辑方式	给药方式	剂量	疾病模型	结果	文献
毛囊MSC	ECM1	慢病毒转染	iv	1×10⁶	肝硬化	抑制HSC活化，减轻肝硬化	［29］
骨髓MSC	Smad7	慢病毒转染	im	（3～5）×10⁶	肝硬化	降低血清Ⅰ型和Ⅲ型胶原酶，抑制TGF-β1信号通路，减轻肝硬化	［31］
胎盘MSC	PRL-1	慢病毒和非病毒转染	iv	2×10⁶	肝硬化	抗MSC凋亡，增强线粒体代谢	［34］
脐带MSC	VEGF165	腺病毒转染	iv	2×10⁶	ALF	增加MSC归巢并促进肝再生	［36］
脐带MSC	CCR2	慢病毒转染	iv	1×10⁶	ALF	MSC向受损靶组织归巢增加并促进肝再生	［37］
脐带MSC	HNF4α	质粒	ip	2×10⁶	ALF	促进M2巨噬细胞极化并减少炎症反应，改善肝衰竭	［38］
脐带MSC	HNF4α	慢病毒转染	iv	1×10⁶	HCC	通过下调 Wnt/β-catenin 信号通路减少肝癌细胞生长和转移，从而抑制HCC进展	［44］
脐带MSC	sFlt-1	慢病毒	iv	6×10⁵	HCC	抑制HCC小鼠模型中的肿瘤生长并延长生存期	［43］
脂肪MSC-exo	miR-4465	非病毒转染	iv	1×10¹²微粒/kg	肝纤维化	靶向LOXL2并抑制HSC激活，减轻肝纤维化	［48］
脐带MSC-exo	miR-27a-3p	非病毒转染	iv	NA	HCC	抑制肝癌细胞增殖、侵袭和转移	［52］
脂肪MSC-exo	miR-199a	慢病毒转染	iv	50 μg	HCC	靶向mTOR通路，增加肝癌细胞对阿霉素敏感性	［55］
注：iv，静脉注射；im，肌内注射；ip，腹腔注射；LOXL2，赖氨酰氧化酶样蛋白2；NA，文中未提及。

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