通过机械力刺激乙型肝炎病毒X基因(<italic style="font-style: italic">HBX</italic>)转染的肝星状细胞制备血液透析用双层仿生血管

刘弘毅; 周媛媛; 郭鹏; 郑雄伟; 陈炜斌; 张世超; 付雨; 周旭; 万郑; 赵斌; 赵一麟

doi:10.1631/jzus.B2300479

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通过机械力刺激乙型肝炎病毒X基因(HBX)转染的肝星状细胞制备血液透析用双层仿生血管

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Research Article | Updated：2024-06-24

通过机械力刺激乙型肝炎病毒X基因(HBX)转染的肝星状细胞制备血液透析用双层仿生血管
Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X (HBX) gene- transfected hepatic stellate cells
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2024年25卷第6期页码：499-512
Affiliations：

1.Department of Oncology and Vascular Interventional Radiology, Zhongshan Hospital Affiliated to Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China
2.School of Medicine, Xiamen University, Xiamen 361102, China
3.Xiamen Health and Medical Big Data Center, Xiamen 361008, China
4.Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma (Zhongshan Hospital Affiliated to Xiamen University), Xiamen 361004, China
5.Xiamen Key Laboratory of Cellular Intervention and Interventional Medical Materials, Xiamen 361004, China
Funds：

the National Natural Science Foundation of China(81770294);the Natural Science Foundation of Fujian Province(2023J05261)
DOI：10.1631/jzus.B2300479
中图分类号：
CSTR：
纸质出版日期： 2024-06-15 ，

网络出版日期： 2024-06-01 ，

收稿日期： 2023-07-10 ，

修回日期： 2023-08-23 ，

刘弘毅,周媛媛,郭鹏等.通过机械力刺激乙型肝炎病毒X基因(HBX)转染的肝星状细胞制备血液透析用双层仿生血管[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(06):499-512.

Hongyi LIU, Yuanyuan ZHOU, Peng GUO, et al. Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X (HBX) gene- transfected hepatic stellate cells[J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2024,25(6):499-512.
刘弘毅,周媛媛,郭鹏等.通过机械力刺激乙型肝炎病毒X基因(HBX)转染的肝星状细胞制备血液透析用双层仿生血管[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(06):499-512. DOI： 10.1631/jzus.B2300479.

Hongyi LIU, Yuanyuan ZHOU, Peng GUO, et al. Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X (HBX) gene- transfected hepatic stellate cells[J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2024,25(6):499-512. DOI： 10.1631/jzus.B2300479.

摘要

人工血管的移植（AVG）造瘘被广泛用于肾衰竭患者的血液透析治疗。然而，目前临床使用的人工血管的弹性和顺应性较差，容易导致狭窄，形成血栓。用于透析的理想人造血管应模拟天然血管的结构和成分，而天然血管主要由血管内细胞分泌的细胞外基质（ECM）中的胶原蛋白维持。研究发现，在乙型肝炎病毒（HBV）诱导的肝纤维化中，肝星状细胞（HSCs）变得异常活跃，并产生过多的 ECM 纤维。此外，机械刺激可促进 ECM分泌并重塑ECM的纤维结构。基于上述因素，我们用乙型肝炎病毒X基因（

HBX

）转染HSCs细胞，在体外模拟HBV病毒感染的过程。随后，将

HBX

-HSCs细胞种植入由聚己内酯-聚氨酯（PCL-PU）制备的内层致密、外层多孔的双层支架，通过机械力刺激

HBX

-HSCs分泌大量的胶原纤维，并促进其与血管支架的多孔结构进行交联。由此，我们获得了一种ECM-PCL-PU复合仿生血管，其在脱细胞后可作为透析用血管。最后，我们将制备得到的血管支架植入兔颈部动静脉瘘模型。该血管支架具有很强的拉伸强度和顺畅的血流，并在兔子体内形成了自体血管。综上，我们的研究展示了利用人体细胞创建仿生透析血管的方法，为创建临床透析血管通路提供了一种新方法。

Abstract

Artificial vascular graft (AVG) fistula is widely used for hemodialysis treatment in patients with renal failure. However

it has poor elasticity and compliance

leading to stenosis and thrombosis. The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery

which is primarily maintained by collagen in the extracellular matrix (ECM) of arterial cells. Studies have revealed that in hepatitis B virus (HBV)-induced liver fibrosis

hepatic stellate cells (HSCs) become hyperactive and produce excessive ECM fibers. Furthermore

mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure. Based on the above factors

we transfected HSCs with the he

patitis B viral X (

HBX

) gene for simulating the process of HBV infection. Subsequently

these

HBX

-HSCs were implanted into a polycaprolactone-polyurethane (PCL-PU) bilayer scaffold in which the inner layer is dense and the outer layer consists of pores

which was mechanically stimulated to promote the secretion of collagen nanofiber from the

HBX

-HSCs and to facilitate crosslinking with the scaffold. We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization. Then

the vessel scaffold was implanted into a rabbit’s neck arteriovenous fistula model. It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit’s body. Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels

providing a novel approach for creating clinical vascular access for dialysis.

关键词

复合双层仿生血管细胞外基质肝星状细胞乙型肝炎病毒X基因（HBX）机械力

Keywords

Composite bilayer bionic blood vesselExtracellular matrix (ECM)Hepatic stellate cells (HSCs)Hepatitis B viral X (HBX)geneMechanical force

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通过机械力刺激乙型肝炎病毒X基因(HBX)转染的肝星状细胞制备血液透析用双层仿生血管

Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X (HBX) gene- transfected hepatic stellate cells

DOI：10.1631/jzus.B2300479

摘要

Abstract

关键词

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