Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Duke Transplant Center, Duke University Medical Center, Durham, NC, USA.
Cell Mol Immunol. 2019 Apr;16(4):334-342. doi: 10.1038/s41423-019-0207-3. Epub 2019 Feb 13.
Newly emerging technologies are rapidly changing conventional approaches to organ transplantation. In the modern era, the key challenges to transplantation include (1) how to best individualize and possibly eliminate the need for life-long immunosuppression and (2) how to expand the donor pool suitable for human transplantation. This article aims to provide readers with an updated review of three new technologies that address these challenges. First, single-cell RNA sequencing technology is rapidly evolving and has recently been employed in settings related to transplantation. The new sequencing data indicate an unprecedented cellular heterogeneity within organ transplants, as well as exciting new molecular signatures involved in alloimmune responses. Second, sophisticated nanotechnology platforms provide a means of therapeutically delivering immune modulating reagents to promote transplant tolerance. Tolerogenic nanoparticles with regulatory molecules and donor antigens are capable of targeting host immune responses with tremendous precision, which, in some cases, results in donor-specific tolerance. Third, CRISPR/Cas9 gene editing technology has the potential to precisely remove immunogenic molecules while inserting desirable regulatory molecules. This technology is particularly useful in generating genetically modified pigs for xenotransplantation to solve the issue of the shortage of human organs. Collectively, these new technologies are positioning the transplant community for major breakthroughs that will significantly advance transplant medicine.
新兴技术正在迅速改变传统的器官移植方法。在现代,移植的主要挑战包括:(1)如何最好地个体化并可能消除对终身免疫抑制的需求,(2)如何扩大适合人类移植的供体库。本文旨在为读者提供对解决这些挑战的三种新技术的最新综述。首先,单细胞 RNA 测序技术正在迅速发展,最近已应用于与移植相关的领域。新的测序数据表明,器官移植内的细胞异质性前所未有,以及涉及同种免疫反应的令人兴奋的新分子特征。其次,复杂的纳米技术平台提供了一种治疗性递送电调控试剂以促进移植耐受的方法。具有调节分子和供体抗原的耐受纳米颗粒能够以极高的精度靶向宿主免疫反应,在某些情况下,导致供体特异性耐受。第三,CRISPR/Cas9 基因编辑技术具有精确去除免疫原性分子同时插入理想的调节分子的潜力。这项技术在产生用于异种移植的基因修饰猪以解决人类器官短缺问题方面特别有用。总的来说,这些新技术使移植界有望取得重大突破,从而极大地推动移植医学的发展。