Nonaka Paula N, Uriarte Juan J, Campillo Noelia, Oliveira Vinicius R, Navajas Daniel, Farré Ramon
Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain.
CIBER Enfermedades Respiratorias, Madrid, Spain.
Respir Res. 2016 Nov 28;17(1):161. doi: 10.1186/s12931-016-0477-6.
A current approach to obtain bioengineered lungs as a future alternative for transplantation is based on seeding stem cells on decellularized lung scaffolds. A fundamental question to be solved in this approach is how to drive stem cell differentiation onto the different lung cell phenotypes. Whereas the use of soluble factors as agents to modulate the fate of stem cells was established from an early stage of the research with this type of cells, it took longer to recognize that the physical microenvironment locally sensed by stem cells (e.g. substrate stiffness, 3D architecture, cyclic stretch, shear stress, air-liquid interface, oxygenation gradient) also contributes to their differentiation. The potential role played by physical stimuli would be particularly relevant in lung bioengineering since cells within the organ are physiologically subjected to two main stimuli required to facilitate efficient gas exchange: air ventilation and blood perfusion across the organ. The present review focuses on describing how the cell mechanical microenvironment can modulate stem cell differentiation and how these stimuli could be incorporated into lung bioreactors for optimizing organ bioengineering.
当前获取生物工程肺作为未来移植替代方案的一种方法是将干细胞接种在脱细胞肺支架上。这种方法中有待解决的一个基本问题是如何驱动干细胞分化为不同的肺细胞表型。虽然从这类细胞研究的早期阶段就开始使用可溶性因子作为调节干细胞命运的试剂，但人们花了更长时间才认识到干细胞局部感知的物理微环境（如底物硬度、三维结构、循环拉伸、剪切应力、气液界面、氧梯度）也有助于它们的分化。物理刺激所起的潜在作用在肺生物工程中可能尤为重要，因为器官内的细胞在生理上会受到促进有效气体交换所需的两种主要刺激：空气通气和器官内的血液灌注。本综述重点描述细胞机械微环境如何调节干细胞分化，以及如何将这些刺激因素纳入肺生物反应器以优化器官生物工程。
