Revascularization of decellularized lung scaffolds: principles and progress.
Revascularization of decellularized lung scaffolds: principles and progress.
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DOI：
10.1152/ajplung.00237.2015
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Collin T. Stabler;S. Lecht;M. Mondrinos;E. Goulart;P. Lazarovici;P. Lelkes
中科院分区：
文献类型：
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作者：
Collin T. Stabler;S. Lecht;M. Mondrinos;E. Goulart;P. Lazarovici;P. Lelkes
对于基于生物技术的新型肺修复和/或替代治疗方法（例如整个生物工程肺的组织工程）的临床需求显然尚未得到满足。最近的研究证明了通过去除所有细胞成分来使整个器官脱细胞的可行性，从而留下细胞外基质作为复杂的三维（3D）仿生支架。植入脱细胞肺支架（DLS），用患者特异性肺（祖细胞）进行再细胞化，被认为是肺移植的最终替代方案。临床前研究表明，在植入啮齿动物模型后，用气道和血管细胞进行再细胞化的生物工程肺能够进行长达 14 天的气体交换。然而，这一概念的长期适用性在一定程度上受到阻碍，因为目前的方法未能重建具有生理功能的静态内皮细胞，该内皮细胞衬在重新接种的肺支架的整个血管树上，正如体内气道室出血和脉管系统血栓形成的发生所推断的那样。在这篇综述中，我们探讨了这样的观点，即成功的全肺生物工程将关键取决于：1）在脱细胞过程中和脱细胞后保持和/或重建内皮下基底膜的完整性，特别是分隔气道和毛细血管的超薄呼吸膜；2）恢复血管生理功能，包括屏障功能和重新接种后内皮衬里的静止状态。 血管室。我们认为，肺血管树的整体生理重建将显着促进下一代生物工程全肺的临床转化。
There is a clear unmet clinical need for novel biotechnology-based therapeutic approaches to lung repair and/or replacement, such as tissue engineering of whole bioengineered lungs. Recent studies have demonstrated the feasibility of decellularizing the whole organ by removal of all its cellular components, thus leaving behind the extracellular matrix as a complex three-dimensional (3D) biomimetic scaffold. Implantation of decellularized lung scaffolds (DLS), which were recellularized with patient-specific lung (progenitor) cells, is deemed the ultimate alternative to lung transplantation. Preclinical studies demonstrated that, upon implantation in rodent models, bioengineered lungs that were recellularized with airway and vascular cells were capable of gas exchange for up to 14 days. However, the long-term applicability of this concept is thwarted in part by the failure of current approaches to reconstruct a physiologically functional, quiescent endothelium lining the entire vascular tree of reseeded lung scaffolds, as inferred from the occurrence of hemorrhage into the airway compartment and thrombosis in the vasculature in vivo. In this review, we explore the idea that successful whole lung bioengineering will critically depend on 1) preserving and/or reestablishing the integrity of the subendothelial basement membrane, especially of the ultrathin respiratory membrane separating airways and capillaries, during and following decellularization and 2) restoring vascular physiological functionality including the barrier function and quiescence of the endothelial lining following reseeding of the vascular compartment. We posit that physiological reconstitution of the pulmonary vascular tree in its entirety will significantly promote the clinical translation of the next generation of bioengineered whole lungs.