複合組織異體移植之新進展

Recent Advances in Vascularized Composite Allotransplantation

複合組織異體移植（vascularized composite allotransplantation, VCA）包括皮膚、肌肉、骨骼、周邊神經和血管等組織同時移植，例如手臂移植、臉移植等，在過去的20年中，人體實驗已成功運用在臨床，證明此技術臨床可行。雖然複合組織異體移植主要是改善病患生活品質，但目前一般治療與單一器官移植（如肝臟，腎臟，心臟等）比較，仍須終生服用較高劑量免疫抑制劑，但長期免疫抑制劑副作用導致併發症仍然是複合組織異體移植的重要障礙。如何克服移植後急性和慢性排斥，並盡量減少免疫抑制劑使用和延長VCA存活為主要課題。文獻以異體移植動物模型做臨床前轉譯研究評估免疫調節方法，包括共刺激阻斷（co-stimulation blockade）、細胞療法，甚至細胞衍生物細胞外囊泡等，在避免排斥甚至產生免疫耐受性已有不少證據，這些免疫策略未來將有機會在臨床移植運用。本篇將回溯VCA近況相關的臨床研究成果及文獻探討免疫策略。

Vascularized composite allotransplantation (VCA), such as hand or face transplantation which included skin, muscle, bone, peripheral nerves and vessels, has been clinical applications for reconstructive microsurgery for two decades. VCA is quite similar to solid organ transplantations which requires the use of systemic immunosuppression in order to prevent acute or chronic rejection and adverse effects. Owing to the high immunogenicity of VCA, patients need to take long-term multiple high dosage immunosuppressive drugs and suffer from side effects although this is an elective surgery to improve quality of life. Therefore, new strategies to prevent the long-term use of immunosuppressants has been developed. Numerous strategies such as new co-stimulation blockade agents, cell-based approaches such as mesenchymal stem cells, regulatory T cells, or even extracellular vesicles have been investigated. Immunotherapy could have the potential to induce immune tolerance toward a transplanted composite tissue and organ. This manuscript reviewed the history of clinical applications in current VCAs and the future potentials of immunomodulation strategies.