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转基因肝细胞针对比利鲁宾和氨代谢,用于构建生物人工肝系统

Ke Wang¹, Yuankui Zhu¹, Mengqing Li²

¹College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Biomaterials research

|July 16, 2024

概括

使用基因工程 SynHeps-II 细胞的新型生物人工肝 (BAL) 在急性肝衰竭 (ALF) 模型中显著降低了有毒代谢物. 这种基于细胞的疗法对ALF患者来说是有前途的,改善了生存率并促进了肝脏的再生.

科学领域:

肝病学和再生医学肝病学和再生医学
生物技术和生物工程生物技术和生物工程

背景情况:

急性肝衰竭 (ALF) 是一种严重的疾病,其特点是肝脏排毒功能受损.
目前对ALF的治疗方法有限,这凸显了对创新的治疗策略的需求.

研究的目的:

开发和评估一种基因工程的基于细胞的生物人工肝 (BAL) 系统,用于治疗ALF.
在ALF模型中评估SynHeps-II细胞系在降低有毒代谢物水平和促进肝脏恢复方面的有效性.

主要方法:

基因修饰HepG2细胞以创建SynHeps-II细胞系,过度表达关键的解毒基因.
在细胞微载体中封装SynHeps-II细胞并组装成与血细胞接触的BAL系统 (PCC-BAL).
使用患者血进行体外试验和使用ALF动物模型进行体内评估,包括体外血液净化.

主要成果:

SynHeps-II细胞在体外和体内显著降低了血清胆红素和氨水平.
嵌入 SynHeps-II 的 PCC-BAL 系统使 ALF 子的存活率提高了 80% 以上.
治疗改善了肝脏和大脑的炎症,减少了氧化应激,减轻了肝脏脑病变,并通过NF-κB和STAT3途径促进了肝脏的再生.

结论:

基于SynHeps-II细胞的BAL系统显示了急性肝衰竭的显著治疗潜力.
开发的PCC-BAL系统适合临床前评估,并显示出临床翻译的前景.
需要进一步的临床试验来验证这种创新的ALF治疗的疗效和安全性.

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