Hamilton N J, Kanani M, Roebuck D J, Hewitt R J, Cetto R, Culme-Seymour E J, Toll E, Bates A J, Comerford A P, McLaren C A, Butler C R, Crowley C, McIntyre D, Sebire N J, Janes S M, O'Callaghan C, Mason C, De Coppi P, Lowdell M W, Elliott M J, Birchall M A
University College London Ear Institute, Royal National Throat Nose and Ear Hospital, London, UK.
Department of Cardiothoracic Surgery, Great Ormond Street Hospital, London, UK.
Am J Transplant. 2015 Oct;15(10):2750-7. doi: 10.1111/ajt.13318. Epub 2015 Jun 2.
In 2010, a tissue-engineered trachea was transplanted into a 10-year-old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti-HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross-sectional area analysis showed restriction of growth within an area of in-stent stenosis. This report demonstrates the long-term viability of a decellularized tissue-engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs.
2010年,一个使用脱细胞的已故供体气管构建的组织工程气管被移植到一名10岁儿童体内,该气管重新植入了受体的呼吸道上皮细胞和间充质基质细胞。我们报告了该儿童4年来的临床进展、气管上皮化情况及费用。事件年表源自临床记录,费用根据每个手术的参考费用确定。对系列气管镜检查图像、肺功能测试和抗人白细胞抗原(HLA)血样进行了比较。检查了上皮形态以及T细胞、Ki67和裂解的半胱天冬酶3活性。计算流体动力学模拟确定了气流、速度和气道压降。移植后的第一年,干预次数减少,该儿童目前临床状况良好,继续接受教育。尽管保留了支架,但内镜检查显示在15个月时黏膜完全覆盖。组织细胞学显示有分化的呼吸层,且无异常免疫活性。计算流体动力学分析表明,气管远端狭窄周围的速度和压降增加。横截面积分析显示支架内狭窄区域的生长受限。本报告证明了脱细胞组织工程气管在儿童体内的长期生存能力。需要进一步开展研究,以开发发病率更低、生物力学性能更好且成本更低的生物工程小儿气管替代物。