Detailed surgical description of porcine vascularized thymus lobe transplantation.

Frontiers in transplantation Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI:10.3389/frtra.2024.1499844
M Esad Gunes, Sho Fujiwara, Daniel H Wolbrom, Alexander Cadelina, Susan Qudus, Dilrukshi Ekanayake-Alper, Dominik Hajosi, David H Sachs, Greg Nowak
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Abstract

Background: 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.

Methods: GalT-KO miniature swine (n = 16) and baboons (n = 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.

Results: We performed non-survival (n = 2) and survival (n = 2) VTL autotransplants in pigs and xeno-VTL and kidney transplants in baboons (n = 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.

Conclusion: 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.

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猪胸腺叶血管化移植的详细手术描述。
背景: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然是移植中的重大挑战。通过胸腺移植培养移植耐受性可能是一个解决方案。本文详细介绍了猪血管化胸腺叶(VTL)的获取和移植技术,该技术可用于大型动物同种异体和异种移植模型的研究。方法:采用GalT-KO小型猪(16头)和狒狒(12头)进行VTL移植。解剖右或左颈胸腺叶,切除其动脉和静脉,并用冷乳酸林格氏液冲洗。所有动物均在腹腔内移植VTL移植物。结果:我们在猪身上进行了非存活(n = 2)和存活(n = 2)自体VTL移植,在狒狒身上进行了异种VTL移植和肾脏移植(n = 12)。所有移植物再灌注后立即呈粉红色,血流进出良好。自体移植存活组的猪由于与VTL捐赠相关的并发症在术后立即安乐死。一只狒狒由于抗体介导的排斥反应失去了移植物,另一只狒狒由于静脉血栓形成而失去了移植物。其他狒狒没有并发症并存活到终点。结论:在此,我们描述了我们在猪胸腺血管化获取和移植方面的方法和经验。该技术需要适度的手术技巧才能获得可重复的结果。由于与收获过程相关的手术并发症的高风险,不建议猪活体捐献VTL。
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