人气道干细胞在肺上皮工程中的再生潜力,Biomaterials

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人气道干细胞在肺上皮工程中的再生潜力
Biomaterials ( IF 12.8 ) Pub Date : 2016-09-12 11:12:33
Sarah E. Gilpin, Jonathan M. Charest, Xi Ren, Luis F. Tapias, Tong Wu, Daniele Evangelista-Leite, Douglas J. Mathisen, Harald C. Ott

用于移植的生物工程器官最终可以为晚期器官衰竭提供个性化解决方案，而没有排斥的风险。建立在全器官灌注脱细胞过程的基础上，我们旨在开发新颖的，可翻译的方法，用于可移植的肺构建体的重新细胞化和再生。我们首先分离出增殖性的KRT5 ⁺ TP63 ⁺人肺组织中的基础上皮干细胞群体，并在常规2D培养中表现出扩展能力。然后，我们在离体全器官培养物中重新填充了脱细胞大鼠支架，并观察到与原发性肺内皮细胞结合的持续细胞增殖。为了显示临床可扩展性，并在人类环境中测试基底细胞群的再生能力，我们然后在仿生条件下对细胞进行了细胞分离和培养。对再生组织构建体的分析证实了培养7天后的细胞活力和持续的代谢活性。组织分析显示组织结构和形态有组织的广泛再细胞化，并保留了基底上皮细胞表型。重新细胞化的肺结构显示动态顺应性和基本的气体交换能力。我们的结果强调了患者来源的人类气道干细胞在肺组织工程中的再生潜力。我们预计这些进展对整个肺生物工程和离体器官修复具有临床意义。

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Regenerative potential of human airway stem cells in lung epithelial engineering

Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularization and regeneration of transplantable lung constructs. We first isolated a proliferative KRT5⁺TP63⁺ basal epithelial stem cell population from human lung tissue and demonstrated expansion capacity in conventional 2D culture. We then repopulated acellular rat scaffolds in ex vivo whole organ culture and observed continued cell proliferation, in combination with primary pulmonary endothelial cells. To show clinical scalability, and to test the regenerative capacity of the basal cell population in a human context, we then recellularized and cultured isolated human lung scaffolds under biomimetic conditions. Analysis of the regenerated tissue constructs confirmed cell viability and sustained metabolic activity over 7 days of culture. Tissue analysis revealed extensive recellularization with organized tissue architecture and morphology, and preserved basal epithelial cell phenotype. The recellularized lung constructs displayed dynamic compliance and rudimentary gas exchange capacity. Our results underline the regenerative potential of patient-derived human airway stem cells in lung tissue engineering. We anticipate these advances to have clinically relevant implications for whole lung bioengineering and ex vivo organ repair.

更新日期：2016-09-13

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