Fries C Anton, Lawson Sharon D, Wang Lin C, Spencer Jerry R, Roth Mark, Rickard Rory F, Gorantla Vijay S, Davis Michael R
59MDW/Science and Technology, Joint Base, San Antonio, TX.
Fred Hutchinson Cancer Research Center, Seattle, WA.
Ann Plast Surg. 2019 Apr;82(4):452-458. doi: 10.1097/SAP.0000000000001693.
Vascularized composite allotransplantation can reconstruct devastating tissue loss by replacing like-with-like tissues, most commonly in the form of hand or face transplantation. Unresolved technical and ethical challenges have meant that such transplants remain experimental treatments. The most significant barrier to expansion of this field is the requirement for systemic immunosuppression, its toxicity and effect on longevity.Hydrogen sulfide (H2S) has been shown experimentally to ameliorate the ischemia reperfusion injury associated with composite tissue autotransplantation, which has been linked to acute rejection in solid organ transplantation. In this protocol, a large-animal model was used to evaluate the effect of H2S on acute rejection after composite tissue allotransplantation.
A musculocutaneous flap model in SLA-mismatched swine was used to evaluate acute rejection of allotransplants in 2 groups: control animals (n = 8) and a treatment group in which the allografts were pretreated with hydrogen sulfide (n = 8). Neither group was treated with systemic immunosuppression. Acute rejection was graded clinically and histopathologically by an independent, blinded pathologist. Data were analyzed by t tests with correction for multiple comparisons by the Holm-Šídák method.
Clinically, H2S-treated tissue composites showed a delay in the onset of rejection that was statistically significant from postoperative day 6. Histopathologically, this difference between groups was also apparent, although evidence of a difference in groups disappeared beyond day 10.
Targeted hydrogen sulfide treatment of vascularized composite allografts immediately before transplantation can delay acute rejection. This may, in turn, reduce or obviate the requirement for systemic immunosuppression.
血管化复合组织异体移植可以通过用相似组织替换来重建严重的组织缺损，最常见的形式是手部或面部移植。尚未解决的技术和伦理挑战意味着此类移植仍然是实验性治疗方法。该领域扩展的最大障碍是全身性免疫抑制的需求、其毒性以及对寿命的影响。实验表明，硫化氢（H₂S）可改善与复合组织自体移植相关的缺血再灌注损伤，而这种损伤与实体器官移植中的急性排斥反应有关。在本方案中，使用大型动物模型评估H₂S对复合组织异体移植后急性排斥反应的影响。
在SLA不匹配的猪中建立肌皮瓣模型，以评估两组异体移植的急性排斥反应：对照组动物（n = 8）和移植前用硫化氢预处理同种异体移植物的治疗组（n = 8）。两组均未接受全身性免疫抑制治疗。由一名独立的、不知情的病理学家对急性排斥反应进行临床和组织病理学分级。数据采用t检验进行分析，并通过Holm-Šídák方法对多重比较进行校正。
临床上，硫化氢处理的组织复合物在术后第6天开始出现排斥反应的时间延迟，具有统计学意义。组织病理学上，两组之间的这种差异也很明显，尽管在第10天之后两组差异的证据消失。
在移植前立即对血管化复合异体移植物进行靶向硫化氢治疗可延迟急性排斥反应。这反过来可能会减少或消除全身性免疫抑制的需求。
