使用转基因异种猪肝与脑死亡人类死者的体外肝脏交叉循环
Abraham Shaked1, Alex Sagar2, Kim M Olthoff3
1Penn Transplant Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. abraham.shaked@uphs.upenn.edu.
Nature medicine
|February 9, 2026
概括
使用转基因猪肝的体外肝脏交叉循环 (ELC) 为肝衰竭提供了一个潜在的解决方案. 这项研究证明了ELC.
科学领域:
- 异种移植研究 异种移植研究
- 器官支持系统 器官支持系统
- 免疫学 免疫学 免疫学
背景情况:
- 急性和急性-慢性肝衰竭存在重大未满足的临床需求.
- 目前的肝脏支持选择有限,需要新的方法.
- 转基因异源性肝脏提供了一种临时性肝脏支持的潜在解决方案.
研究的目的:
- 通过使用转基因猪肝来评估体外肝脏交叉循环 (ELC) 期间的早期免疫反应.
- 在人类死者模型中评估异种猪肝提供的生理支持.
- 为了确定ELC的可行性与最小的免疫抑制.
主要方法:
- 四名人类死者用转基因猪肝进行了ELC (三重甘氨酸淘汰,七个人类转基因,PERVs被禁用).
- 通过静脉注射甲基prednisolone实现了免疫抑制.
- 进行了ELC72-84小时 (本地肝脏 in situ) 或48小时 (肝切除术后,仅异种肝脏).
主要成果:
- 异种肝脏显示保存的结构,轻微的免疫透和IgM沉积.
- 猪肝产生胆汁,并补充了原生肝细胞功能.
- 在异源性肝脏单独模型中,血动力学稳定性和代谢功能得到维持.
结论:
- 通过使用转基因猪肝进行体外肝脏交叉循环 (ELC) 是可行的.
- 对于有效的异源性肝脏支持,最少的免疫抑制是必要的.
- 作为一种有效的临时肝脏支持策略,ELC显示出潜在的潜力.
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