Department of Urology, School of Medicine, China Medical University and Hospital, Taichung, Taiwan.
Animal Technology Research Center/Division of Animal Technology, Agriculture Technology Research Institute, Miaoli, Taiwan.
Cell Transplant. 2021 Jan-Dec;30:9636897211011995. doi: 10.1177/09636897211011995.
The utilization of biologically produced cells to treat diseases is a revolutionary invention in modern medicine after chemically synthesized small molecule drugs and biochemically made protein drugs. Cells are basic units of life with diverse functions in mature and developing organs, which biological properties could be utilized as a promising therapeutic approach for currently intractable and incurable diseases. Xenogeneic cell therapy utilizing animal cells other than human for medicinal purpose has been studied as a new way of treating diseases. Xenogeneic cell therapy is considered as a potential regenerative approach to fulfill current unmet medical needs because xenogeneic cells could be isolated from different animal organs and expanded ex vivo as well as maintain the characteristics of original organs, providing a versatile and plenty cell source for cell-based therapeutics beside autologous and allogeneic sources. The swine species is considered the most suitable source because of the similarity with humans in size and physiology of many organs in addition to the economic and ethical reasons plus the possibility of genetic modification. This review discusses the old proposed uses of xenogeneic cells such as xenogeneic pancreatic islet cells, hepatocytes and neuronal cells as a living drug for the treatment of degenerative and organ failure diseases. Novel applications of xenogeneic mesenchymal stroma cells and urothelial cells are also discussed. There are formidable immunological barriers toward successful cellular xenotransplantation in clinic despite major progress in the development of novel immunosuppression regimens and genetically multimodified donor pigs. However, immunological barriers could be turn into immune boosters by using xenogeneic cells of specific tissue types as a novel immunotherapeutic agent to elicit bystander antitumor immunity due to rejection immune responses. Xenogeneic cells have the potential to become a safe and efficacious option for intractable diseases and hard-to-treat cancers, adding a new class of cellular medicine in our drug armamentarium.
利用生物产生的细胞来治疗疾病是继化学合成小分子药物和生物化学制造的蛋白质药物之后,现代医学的一项革命性发明。细胞是生命的基本单位,在成熟和发育中的器官中具有多种功能,其生物学特性可被用作治疗目前难以治愈和不可治愈疾病的有前途的治疗方法。利用除人类以外的动物细胞进行治疗目的的异种细胞治疗已被研究作为一种治疗疾病的新方法。异种细胞治疗被认为是一种潜在的再生方法,可以满足当前未满足的医疗需求,因为可以从不同的动物器官中分离出异种细胞,并在体外进行扩增,同时保持原始器官的特性,为细胞治疗提供除自体和同种异体来源之外的多功能和丰富的细胞来源。猪种被认为是最合适的来源,因为除了经济和伦理原因以及遗传修饰的可能性外,许多器官的大小和生理学与人类相似。本文讨论了异种细胞的旧有应用,如异种胰岛细胞、肝细胞和神经元细胞作为治疗退行性和器官衰竭疾病的活体药物。还讨论了异种间充质基质细胞和尿路上皮细胞的新应用。尽管在开发新型免疫抑制方案和基因多修饰供体猪方面取得了重大进展,但在临床中成功进行细胞异种移植仍然存在巨大的免疫障碍。然而,通过使用特定组织类型的异种细胞作为新型免疫治疗剂来引发旁观者抗肿瘤免疫,免疫障碍可以转化为免疫增强剂,因为排斥免疫反应。异种细胞有可能成为治疗难治性疾病和难治疗癌症的安全有效选择,为我们的药物武器库增加了一类新的细胞药物。