Gunes M Esad, Fujiwara Sho, Wolbrom Daniel H, Cadelina Alexander, Qudus Susan, Ekanayake-Alper Dilrukshi, Hajosi Dominik, Sachs David H, Nowak Greg
Columbia Center of Translational Immunology, Columbia University, New York, NY, United States.
Department of Surgery, Columbia University, New York, NY, United States.
Front Transplant. 2024 Nov 22;3:1499844. doi: 10.3389/frtra.2024.1499844. eCollection 2024.
Despite advances in immunosuppressive therapies, chronic rejection and immunosuppression-related complications remain significant challenges in transplantation. Developing transplantation tolerance through thymus transplantation may offer a solution. This paper details our technique for procuring and transplanting porcine vascularized thymic lobes (VTL), which can be utilized to study and research allogeneic and xenogeneic transplantation models in large animals.
GalT-KO miniature swine ( = 16) and baboons ( = 12) were used for VTL transplantation. The right or left cervical thymic lobe was dissected, harvested with its artery and veins, and flushed with cold lactated Ringer's solution. VTL graft was transplanted intraabdominally in all animals.
We performed non-survival ( = 2) and survival ( = 2) VTL autotransplants in pigs and xeno-VTL and kidney transplants in baboons ( = 12). All grafts immediately turned pink after reperfusion and had good blood inflow and outflow. Pigs in the survival autotransplant group were euthanized immediately post-operatively due to complications related to VTL donation. One baboon lost its graft due to antibody-mediated rejection, and another lost it due to venous thrombosis. Other baboons had no complications and survived until the endpoint.
Here, we describe our approach and experience in swine vascularized thymic lobe procurement and transplantation. The technique requires moderate surgical skills to achieve reproducible results. Living-donor VTL donation in pigs is not recommended due to the high risk of surgical complications related to the harvesting procedure.
尽管免疫抑制疗法取得了进展，但慢性排斥反应和免疫抑制相关并发症仍是移植领域的重大挑战。通过胸腺移植诱导移植耐受可能提供一种解决方案。本文详细介绍了我们获取和移植猪血管化胸腺叶（VTL）的技术，该技术可用于研究大型动物的同种异体和异种移植模型。
使用GalT-KO小型猪（n = 16）和狒狒（n = 12）进行VTL移植。解剖右侧或左侧颈胸腺叶，连同其动静脉一起收获，并用冷乳酸林格氏液冲洗。在所有动物中，将VTL移植物腹腔内移植。
我们在猪身上进行了非存活（n = 2）和存活（n = 2）的VTL自体移植，在狒狒身上进行了异种VTL和肾脏移植（n = 12）。所有移植物再灌注后立即变红，血流进出良好。存活自体移植组的猪术后因与VTL供体相关的并发症立即实施安乐死。一只狒狒因抗体介导的排斥反应失去了移植物，另一只因静脉血栓形成失去了移植物。其他狒狒没有并发症，存活至实验终点。
在此，我们描述了我们在猪血管化胸腺叶获取和移植方面的方法和经验。该技术需要一定的手术技巧才能获得可重复的结果。由于与获取过程相关的手术并发症风险高，不建议在猪身上进行活体供体VTL捐献。
