Tracheal Replacement Therapy with a Stem Cell-Seeded Graft: Lessons from Compassionate Use Application of a GMP-Compliant Tissue-Engineered Medicine.
Tracheal Replacement Therapy with a Stem Cell-Seeded Graft: Lessons from Compassionate Use Application of a GMP-Compliant Tissue-Engineered Medicine.
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DOI：
10.1002/sctm.16-0443
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发表时间：
2017-06
影响因子：
6
通讯作者：
Birchall MA
中科院分区：
文献类型：
--
作者：
Elliott MJ;Butler CR;Varanou-Jenkins A;Partington L;Carvalho C;Samuel E;Crowley C;Lange P;Hamilton NJ;Hynds RE;Ansari T;Sibbons P;Fierens A;McLaren C;Roebuck D;Wallis C;Muthialu N;Hewitt R;Crabbe D;Janes SM;De Coppi P;Lowdell MW;Birchall MA
气管置换术治疗终末期气道疾病仍然是一个难以实现的目标。在富有同情心的用例中使用组织工程气管表明，这种方法是可行的选择。在本研究中，我们对一名在传统气管重建技术失败后出现严重气管狭窄的女孩进行了干细胞播种、去细胞组织工程气管移植。该移植物代表了第一个完全符合GMP标准的细胞种子气管移植物。我们报告该病例的重要临床前和临床数据，该病例以接受者死亡告终。早期的结果是令人鼓舞的，但是一个急性事件，假设是胸内出血，在移植后3周引起突发性气道阻塞，导致她死亡。我们详细介绍了临床事件，并确定了优先改善未来移植的领域。特别是，我们提倡在植入后的头几个月使用支架。该病例的负面结果突出了临床翻译的固有困难，临床前体内模型无法复制所遇到的复杂临床场景。提供GMP移植物的实际困难强调了完善I期临床试验方案的必要性。干细胞转化医学2017；6:1458 - 1464
Tracheal replacement for the treatment of end‐stage airway disease remains an elusive goal. The use of tissue‐engineered tracheae in compassionate use cases suggests that such an approach is a viable option. Here, a stem cell‐seeded, decellularized tissue‐engineered tracheal graft was used on a compassionate basis for a girl with critical tracheal stenosis after conventional reconstructive techniques failed. The graft represents the first cell‐seeded tracheal graft manufactured to full good manufacturing practice (GMP) standards. We report important preclinical and clinical data from the case, which ended in the death of the recipient. Early results were encouraging, but an acute event, hypothesized to be an intrathoracic bleed, caused sudden airway obstruction 3 weeks post‐transplantation, resulting in her death. We detail the clinical events and identify areas of priority to improve future grafts. In particular, we advocate the use of stents during the first few months post‐implantation. The negative outcome of this case highlights the inherent difficulties in clinical translation where preclinical in vivo models cannot replicate complex clinical scenarios that are encountered. The practical difficulties in delivering GMP grafts underscore the need to refine protocols for phase I clinical trials. Stem Cells Translational Medicine 2017;6:1458–1464
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发表时间：
2010-02-01
影响因子：
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作者：
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