Centre for Values, Ethics and the Law in Medicine, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Intern Med J. 2016 Sep;46(9):1017-22. doi: 10.1111/imj.13183.
In Australia, and internationally, the shortage of organ and tissue donors significantly limits the number of patients with critical organ or tissue failure who are able to receive a transplant each year. The rationale for xenotransplantation - the transplantation of living cells, tissues or organs from one species to another - is to meet this shortfall in human donor material. While early clinical trials showed promise, particularly in patients with type I diabetes whose insulin dependence could be temporarily reversed by the transplantation of porcine islet cells, these benefits have been balanced with scientific, clinical and ethical concerns revolving around the risks of immune rejection and the potential transmission of porcine endogenous retroviruses or other infectious agents from porcine grafts to human recipients. However, the advent of CRISPR/Cas9, a revolutionary gene editing technology, has reignited interest in the field with the possibility of genetically engineering porcine organs and tissues that are less immunogenic and have virtually no risk of transmission of porcine endogenous retroviruses. At the same time, CRISPR/Cas9 may also open up a myriad of possibilities for tissue engineering and stem cell research, which may complement xenotransplantation research by providing an additional source of donor cells, tissues and organs for transplantation into patients. The recent international symposium on gene editing, organised by the US National Academy of Sciences, highlights both the enormous therapeutic potential of CRISPR/Cas9 and the raft of ethical and regulatory challenges that may follow its utilisation in transplantation and in medicine more generally.
在澳大利亚和国际上,器官和组织捐献者的短缺严重限制了每年能够接受移植的患有严重器官或组织衰竭的患者数量。异种移植的基本原理——将来自一个物种的活细胞、组织或器官移植到另一个物种中——是为了弥补人类供体材料的短缺。虽然早期的临床试验显示出了希望,特别是在 I 型糖尿病患者中,猪胰岛细胞的移植可以暂时逆转他们对胰岛素的依赖,但这些益处与围绕免疫排斥风险和猪内源性逆转录病毒或其他感染性病原体从猪移植物向人类受者传播的科学、临床和伦理问题相平衡。然而,CRISPR/Cas9 的出现,一种革命性的基因编辑技术,重新激发了人们对该领域的兴趣,有可能对猪器官和组织进行基因工程改造,使其免疫原性降低,几乎没有传播猪内源性逆转录病毒的风险。与此同时,CRISPR/Cas9 也可能为组织工程和干细胞研究开辟无数可能性,这可能通过为移植到患者体内的供体细胞、组织和器官提供额外来源,补充异种移植研究。最近由美国国家科学院组织的国际基因编辑研讨会强调了 CRISPR/Cas9 的巨大治疗潜力,以及在移植和更广泛的医学中使用它可能带来的一系列伦理和监管挑战。