Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, United States of America; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, United States of America; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, United States of America; NorthStar Genomics, Eagan, MN, United States of America.
Departments of Surgery, Columbia Center for Translational Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States of America.
J Mol Cell Cardiol. 2022 Nov;172:109-119. doi: 10.1016/j.yjmcc.2022.07.013. Epub 2022 Aug 27.
End stage heart failure is a terminal disease, and the only curative therapy is orthotopic heart transplantation. Due to limited organ availability, alternative strategies have received intense interest for treatment of patients with advanced heart failure. Recent studies using gene-edited porcine organs suggest that cardiac xenotransplantation may provide a future source of organs. In this review, we highlight the historical milestones for cardiac xenotransplantation and the gene editing strategies designed to overcome immunological barriers, which have culminated in a recent cardiac pig-to-human xenotransplant. We also discuss recent results of studies on the engineering of human-porcine chimeric organs that may provide an alternative and complementary strategy to overcome some of the major immunological barriers to producing a new source of transplantable organs.
终末期心力衰竭是一种终末期疾病,唯一的根治性治疗方法是原位心脏移植。由于器官来源有限,替代策略受到了广泛关注,以治疗晚期心力衰竭患者。最近使用基因编辑猪器官的研究表明,心脏异种移植可能成为未来器官的来源。在这篇综述中,我们重点介绍了心脏异种移植的历史里程碑和设计用于克服免疫障碍的基因编辑策略,这些策略最终促成了最近的心脏猪到人的异种移植。我们还讨论了在工程化人-猪嵌合器官方面的最新研究结果,这可能是克服产生新的可移植器官的主要免疫障碍的一种替代和互补策略。