异种肺移植临床前研究进展及单中心技术经验

Progress in preclinical studies of xenogeneic lung transplantation and single-center technical experience

  • 摘要: 肺移植是间质性肺炎、慢性阻塞性肺病、尘埃沉着病等肺部疾病终末期最终的治疗手段。目前,同种异体肺源的短缺大大限制了终末期肺病患者获得肺移植的机会。近年来,随着生物医学工程技术的快速发展,特别是基因修饰和克隆技术的重大突破,异种肺移植展现出重要的临床转化潜力。其中,基因修饰猪因其器官大小、生理特性与人较为接近,且可进行定向基因敲除(如α-Gal抗原敲除)以减少超急性排斥反应的发生,成为最具潜力的异种肺源。本文聚焦于猪异种肺移植的研究进展,系统综述其动物实验及人体试验最新成果及挑战,同时结合深圳市第三人民医院的实践探索,介绍本中心在猪-猴异种肺移植模型中积累的技术经验,以期为该领域的未来研究提供实践借鉴与参考。

     

    Abstract: Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

     

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