Yamada Kazuhiko, Shah Jigesh A, Tanabe Tatsu, Lanaspa Miguel A, Johnson Richard J
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.
Transplantation Biology Research Laboratories, Massachusetts general Hospital, Harvard Medical School, Boston, MA.
Curr Transplant Rep. 2017 Jun;4(2):101-109. doi: 10.1007/s40472-017-0149-6. Epub 2017 May 8.
Inter-species transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors.
Advances in gene editing technology have allowed for the efficient production of multi-transgenic porcine donors leading improved xenograft survival in baboons, up to 2-years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for >6 months survival of a life-supporting kidney with further approaches currently underway to address the challenges mentioned above.
Our recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation.
种间移植,即异种移植,正成为解决器官短缺危机的一种现实策略。在此,我们重点关注推动异种移植研究的重要出版物,以及最近发表的文献和未来的努力方向。
基因编辑技术的进步使得高效生产多转基因猪供体成为可能,这提高了狒狒体内异种移植物的存活率,异位心脏异种移植后长达2年,维持生命的肾脏异种移植后从数周延长至数月。随着技术的发展,出现了更多挑战,包括蛋白尿的出现、与猪巨细胞病毒相关的早期移植物丢失、供体和受体之间器官生长的差异以及高剂量持续免疫抑制的需求。为解决这些问题,我们实验室开发了一种诱导耐受的方案,使维持生命的肾脏存活超过6个月,目前正在采取进一步措施应对上述挑战。
本文所综述的我们最近的发现促使我们开发克服障碍的方法,这些方法与其他人的工作相结合,对异种移植未来的临床应用很有前景。