Tsuchiya Tomoshi, Doi Ryoichiro, Obata Tomohiro, Hatachi Go, Nagayasu Takeshi
Department of Surgical Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Division of Nucleic Acid Drug Development, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan.
Front Bioeng Biotechnol. 2020 Feb 21;8:105. doi: 10.3389/fbioe.2020.00105. eCollection 2020.
Biomaterials have been used for a long time in the field of medicine. Since the success of "tissue engineering" pioneered by Langer and Vacanti in 1993, tissue engineering studies have advanced from simple tissue generation to whole organ generation with three-dimensional reconstruction. Decellularized scaffolds have been widely used in the field of reconstructive surgery because the tissues used to generate decellularized scaffolds can be easily harvested from animals or humans. When a patient's own cells can be seeded onto decellularized biomaterials, theoretically this will create immunocompatible organs generated from allo- or xeno-organs. The most important aspect of lung tissue engineering is that the delicate three-dimensional structure of the organ is maintained during the tissue engineering process. Therefore, organ decellularization has special advantages for lung tissue engineering where it is essential to maintain the extremely thin basement membrane in the alveoli. Since 2010, there have been many methodological developments in the decellularization and recellularization of lung scaffolds, which includes improvements in the decellularization protocols and the selection and preparation of seeding cells. However, early transplanted engineered lungs terminated in organ failure in a short period. Immature vasculature reconstruction is considered to be the main cause of engineered organ failure. Immature vasculature causes thrombus formation in the engineered lung. Successful reconstruction of a mature vasculature network would be a major breakthrough in achieving success in lung engineering. In order to regenerate the mature vasculature network, we need to remodel the vascular niche, especially the microvasculature, in the organ scaffold. This review highlights the reconstruction of the vascular niche in a decellularized lung scaffold. Because the vascular niche consists of endothelial cells (ECs), pericytes, extracellular matrix (ECM), and the epithelial-endothelial interface, all of which might affect the vascular tight junction (TJ), we discuss ECM composition and reconstruction, the contribution of ECs and perivascular cells, the air-blood barrier (ABB) function, and the effects of physiological factors during the lung microvasculature repair and engineering process. The goal of the present review is to confirm the possibility of success in lung microvascular engineering in whole organ engineering and explore the future direction of the current methodology.
生物材料在医学领域的应用由来已久。自1993年兰格（Langer）和瓦坎蒂（Vacanti）开创“组织工程”取得成功以来，组织工程研究已从简单的组织生成发展到通过三维重建实现全器官生成。去细胞支架已广泛应用于重建外科领域，因为用于制备去细胞支架的组织可以很容易地从动物或人体获取。当患者自身的细胞接种到去细胞生物材料上时，理论上这将创建由同种异体或异种器官生成的免疫相容性器官。肺组织工程最重要的方面是在组织工程过程中维持器官精细的三维结构。因此，器官去细胞化对于肺组织工程具有特殊优势，因为在肺组织工程中维持肺泡中极薄的基底膜至关重要。自2010年以来，肺支架的去细胞化和再细胞化在方法学上有了许多进展，包括去细胞化方案的改进以及接种细胞的选择和制备。然而，早期移植的工程肺在短期内以器官衰竭告终。不成熟的血管重建被认为是工程器官衰竭的主要原因。不成熟的血管会导致工程肺中形成血栓。成功重建成熟的血管网络将是肺工程取得成功的一项重大突破。为了再生成熟的血管网络，我们需要重塑器官支架中的血管微环境，尤其是微血管。本综述重点介绍去细胞肺支架中血管微环境的重建。由于血管微环境由内皮细胞（ECs）、周细胞、细胞外基质（ECM）以及上皮 - 内皮界面组成，所有这些都可能影响血管紧密连接（TJ），因此我们讨论了ECM的组成和重建、ECs和血管周围细胞的作用、气血屏障（ABB）功能以及肺微血管修复和工程过程中生理因素的影响。本综述的目的是确认在全器官工程中肺微血管工程取得成功的可能性，并探索当前方法的未来方向。
