Kim Minhyung, Fisher Daniel T, Powers Colin A, Repasky Elizabeth A, Skitzki Joseph J
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY.
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY.
Transplant Direct. 2018 Feb 2;4(2):e345. doi: 10.1097/TXD.0000000000000756. eCollection 2018 Feb.
Vascularized composite tissue allotransplantation (VCA) from a cadaveric donor has now become a clinical reality and the treatment modality of choice for patients with devastating injuries, deformities, and complex tissue defects. However, many VCA patients experience severe toxicities due to the strong immunosuppression required secondary to high antigenicity of the grafts. To improve immunosuppressive protocols for VCA, feasible and reliable preclinical models are necessary. The purpose of this study was to introduce new techniques to an established preclinical VCA model to accelerate future investigations.
C57BL/6 (H-2) and BALB/c (H-2) mice were used to perform VCA as recipients and donors, respectively. Surgery time, success rate, associated complications, and mortality were analyzed. Blood flow in grafts was interrogated with laser speckle image (LSI).
A nonsuture cuff technique was used with the abdominal aorta for end-to-end anastomosis. The cuff technique demonstrated efficiency for donor surgery (52 ± 10 minutes for donor vs. 45 ± 8 minutes for recipient surgery). Successful revascularization was achieved in 27 (90%) of 30 transplants. The majority of surgical complications occurred within 48 hours including artery occlusion, venous occlusion, cerebral stroke, and minor bleeding without mortality. LSI was useful in detecting intraoperative vascular complications with display patterns predictive of complication type.
The described techniques may facilitate a more efficient heterotopic hind limb transplantation mouse model of VCA.
来自尸体供体的血管化复合组织异体移植(VCA)现已成为临床现实,是严重创伤、畸形和复杂组织缺损患者的首选治疗方式。然而,许多VCA患者由于移植物高抗原性需要强烈免疫抑制,从而出现严重毒性。为了改进VCA的免疫抑制方案,可行且可靠的临床前模型是必要的。本研究的目的是将新技术引入已建立的临床前VCA模型,以加速未来的研究。
分别使用C57BL/6(H-2)和BALB/c(H-2)小鼠作为受体和供体进行VCA。分析手术时间、成功率、相关并发症和死亡率。用激光散斑图像(LSI)检测移植物中的血流。
采用非缝合袖套技术将腹主动脉进行端端吻合。袖套技术显示出供体手术的效率(供体手术时间为52±10分钟,受体手术时间为45±8分钟)。30例移植中有27例(90%)成功实现血管再通。大多数手术并发症发生在48小时内,包括动脉闭塞、静脉闭塞、脑卒中和少量出血,无死亡病例。LSI有助于检测术中血管并发症,其显示模式可预测并发症类型。
所描述的技术可能有助于建立一个更有效的VCA异位后肢移植小鼠模型。