Cell replacement in human lung bioengineering
Cell replacement in human lung bioengineering
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DOI：
10.1016/j.healun.2018.11.007
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发表时间：
2019-02-01
影响因子：
8.9
通讯作者：
Bacchetta, Matthew
中科院分区：
文献类型：
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作者：
Guenthart, Brandon A.;O'Neill, John D.;Bacchetta, Matthew
背景技术背景：随着终末期肺病患者数量的持续增加，越来越需要增加可用于移植的有限数量的肺。不幸的是，重新设计功能性肺的尝试并不成功，并且人工机械装置作为移植的桥梁的实用性有限。这种困难在很大程度上是由于肺的大小和固有的复杂性，但是，最近的进展，以细胞为基础的治疗提供了一个独特的机会，以提高传统的组织工程方法与有针对性的网站和细胞特异性strategies. METHODS：人肺被认为不适合移植采购和支持使用新的插管技术和修改的离体肺灌注。使用去细胞化溶液的气管内递送来治疗靶向肺区域。标记的间充质干细胞或气道上皮细胞，然后送入肺和孵育长达6 hours. Results：组织样本收集在定期的时间间隔和详细的组织学和免疫组化分析进行评估的有效性，天然细胞去除和外源性细胞替代。区域性脱细胞导致去除气道上皮，保留血管内皮和细胞外基质蛋白。孵育后，交付的细胞被保留在肺中，并表现出均匀的地形分布和扁平的细胞morphology.CONCLUSIONS：我们的研究结果表明，体外器官靶向细胞置换是可行的，并可能最终导致嵌合器官适合移植或发展原位干预治疗或逆转疾病，最终否定移植的需要。(C)2018年国际心肺移植学会。All rights reserved.
BACKGROUND: As the number of patients with end-stage lung disease continues to rise, there is a growing need to increase the limited number of lungs available for transplantation. Unfortunately, attempts at engineering functional lung de novo have been unsuccessful, and artificial mechanical devices have limited utility as a bridge to transplant. This difficulty is largely due to the size and inherent complexity of the lung; however, recent advances in cell-based therapeutics offer a unique opportunity to enhance traditional tissue-engineering approaches with targeted site-and cell-specific strategies.METHODS: Human lungs considered unsuitable for transplantation were procured and supported using novel cannulation techniques and modified ex-vivo lung perfusion. Targeted lung regions were treated using intratracheal delivery of decellularization solution. Labeled mesenchymal stem cells or airway epithelial cells were then delivered into the lung and incubated for up to 6 hours.RESULTS: Tissue samples were collected at regular time intervals and detailed histologic and immunohistochemical analyses were performed to evaluate the effectiveness of native cell removal and exogenous cell replacement. Regional decellularization resulted in the removal of airway epithelium with preservation of vascular endothelium and extracellular matrix proteins. After incubation, delivered cells were retained in the lung and showed homogeneous topographic distribution and flattened cellular morphology.CONCLUSIONS: Our findings suggest that targeted cell replacement in extracorporeal organs is feasible and may ultimately lead to chimeric organs suitable for transplantation or the development of in-situ interventions to treat or reverse disease, ultimately negating the need for transplantation. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.