In Vivo Tissue Engineering of Human Airways
In Vivo Tissue Engineering of Human Airways
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DOI：
10.1016/j.athoracsur.2016.11.027
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发表时间：
2017-05-01
影响因子：
4.6
通讯作者：
Petite, Herve
中科院分区：
文献类型：
--
作者：
Martinod, Emmanuel;Paquet, Joseph;Petite, Herve
背景。气道移植仍然是胸外科的一个主要挑战。基于我们之前的实验室工作，我们开发了使用低温保存的同种异体主动脉作为生物基质在体内生物工程制造气管替代物所需的技术（使用低温保存的同种异体动脉移植物[气管-支气管]研究，NCT01331863）。我们在此报告2例因传统治疗难治性复杂喉气管狭窄而行气管切开术的患者。根据我们的方案，使用性别不匹配的-80℃低温保存主动脉异体移植物支架进行气道重建。随访评估定期使用临床、影像学和内窥镜评估。在支架取出时使用移植物活检标本进行免疫组织化学和XX/XY嵌合研究。研究了移植基质的趋化和血管生成特性。最长随访5年7个月，患者呼吸和说话正常，未行气管切开术或支架置入。II型胶原蛋白和Sox9特异性标记物的免疫检测阳性表明主动脉瓣内软骨再生。从新组织样本的嵌合研究表明再生软骨来自于受体细胞。剩余的有活力的基质细胞释放出与功能相关的促血管生成、趋化、促炎/免疫调节细胞因子和生长因子。本报告证明了体内组织工程用于人类长期功能性气道移植的可行性。(C) 2017年由胸外科医师协会发布
Background. Airway transplantation remains a major challenge in thoracic surgery. Based on our previous laboratory work, we developed the techniques required to bioengineer a tracheal substitute in vivo using cryopreserved aortic allografts as biological matrices (Replacement of the Airways and/or the Pulmonary Vessels Using a Cryopreserved Arterial Allograft [TRACHEO-BRONCART] Study, NCT01331863). We present here 2 patients who had a definitive tracheostomy for complex laryngotracheal stenoses refractory to conventional therapy.Methods. According to our protocol, a stented gender-mismatched -80 degrees C cryopreserved aortic allograft was used for airway reconstruction. Follow-up assessments were done at regular intervals using clinical, imaging, and endoscopic evaluations. Immunohistochemical and XX/XY chimerism studies were performed at time of stent removal using graft biopsy specimens. Chemotactic and angiogenic properties of implanted matrices were also investigated.Results. At a maximal follow-up of 5 years and 7 months, the patients were breathing and speaking normally, without tracheostomy or stent. Regeneration of cartilage within the aortic grafts was demonstrated by positive immunodetection of type II collagen and markers specific for Sox9. Chimerism study from samples of neotissues demonstrated that regenerated cartilage came from recipient cells. The remaining viable matrix cells released a functionally relevant amount of proangiogenic, chemoattractant, proinflammatory/immunomodulatory cytokines, and growth factors.Conclusions. This report documents the feasibility of in vivo tissue engineering for long-term functional airway transplantation in humans. (C) 2017 by The Society of Thoracic Surgeons