Waldner Matthias, Elgendy Tarek Y, Kim Deokyeol Y, Öksüz Sinan, Schweizer Riccardo, Zhang Wensheng, Minervini Marta I, Komatsu Chiaki, Plock Jan A, Gorantla Vijay S, Washington Kia M, Thomson Angus W, Solari Mario G
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; Departement of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, ZH, Switzerland.
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
J Surg Res. 2020 Oct;254:175-182. doi: 10.1016/j.jss.2020.04.026. Epub 2020 May 22.
Vascularized composite tissue allotransplantation (VCA) opens new possibilities for reconstruction of complex tissue defects, including upper extremity and facial transplantation. The main challenges in VCA transplantation are the side effects of long-term immunosuppression and chronic graft rejection. Translational preclinical animal models are crucial for VCA research to improve clinical outcomes and to study underlying immunologic mechanisms. Herein, we describe a novel, large animal, non-bone-bearing VCA model in inbred, swine leukocyte antigen-typed miniature swine.
Transplantation of vertical rectus abdominis myocutaneous (VRAM) flaps was performed between fully swine leukocyte antigen-mismatched miniature swine. The flaps were transferred to the posterolateral aspect of the neck of recipients and anastomosed to the common carotid artery and internal jugular vein. Different immunosuppressive drug regimens were used. Clinical graft evaluation was performed daily, and punch biopsies were taken for histology.
Ten VRAM transplants were performed. The mean ischemia time was 89.4 min (SD ± 47), mean pedicle length 7.5 cm (SD ± 2), mean venous diameter 2.5 mm (SD ± 0.4), and mean arterial diameter 2.2 mm (SD ± 0.3). Follow-up demonstrated good correlation between clinical appearance and progression of graft rejection confirmed by histologic assessment. Complications were intraoperative cardiac arrest in one recipient and one flap loss due to venous compromise.
VRAM transplantation in miniature swine is an appropriate preclinical VCA model, with the advantage of good clinical and histologic correlation during the course of rejection, as well as easy access to the graft. The availability of inbred, haplotyped animals allows studies across different major histocompatibility complex barriers in a non-bone-bearing VCA.
血管化复合组织异体移植（VCA）为包括上肢和面部移植在内的复杂组织缺损重建开辟了新的可能性。VCA移植的主要挑战是长期免疫抑制的副作用和慢性移植物排斥反应。转化性临床前动物模型对于VCA研究改善临床结果和研究潜在免疫机制至关重要。在此，我们描述了一种在近交、猪白细胞抗原分型的小型猪中建立的新型大型动物非带骨VCA模型。
在完全猪白细胞抗原不匹配的小型猪之间进行腹直肌垂直肌皮（VRAM）皮瓣移植。将皮瓣转移至受体颈部后外侧，与颈总动脉和颈内静脉吻合。使用了不同的免疫抑制药物方案。每天进行临床移植物评估，并取穿刺活检进行组织学检查。
进行了10例VRAM移植。平均缺血时间为89.4分钟（标准差±47），平均蒂长7.5厘米（标准差±2），平均静脉直径2.5毫米（标准差±0.4），平均动脉直径2.2毫米（标准差±0.3）。随访显示临床外观与组织学评估证实的移植物排斥进展之间具有良好的相关性。并发症包括1例受体术中心脏骤停和1例因静脉受压导致的皮瓣丢失。
小型猪VRAM移植是一种合适的临床前VCA模型，具有在排斥过程中临床与组织学相关性良好以及易于获取移植物的优点。近交、单倍型动物的可用性使得能够在非带骨VCA中跨越不同的主要组织相容性复合体屏障进行研究。
