Research Topic

Lung Microvascular Niche, Repair and Engineering

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Chronic lung disease is one of the few causes of death that is actually increasing in the Western World. Chronic lung disease typically involves derangements of the alveolar environment, of which the lung microvasculature is a critical component. Changes in lung microvascular niche, such as flow rates and ...

Chronic lung disease is one of the few causes of death that is actually increasing in the Western World. Chronic lung disease typically involves derangements of the alveolar environment, of which the lung microvasculature is a critical component. Changes in lung microvascular niche, such as flow rates and patterns, oxygen tension, cytokine concentrations, and extracellular matrix can result in vascular barrier damage, leukocyte adhesion, platelet aggregation, and further disease progression. Under physiological niche conditions such as laminar flow and stimulation with anti-inflammatory cytokines (e.g. IL6, IL10), the microvasculature synthesizes factors (e.g. nitric oxide, prostacyclin, thrombomodulin) to control thromboresistance, barrier function, and vessel wall inflammation. In contrast, under pathophysiological niche conditions such as non-laminar flow, and pro-inflammatory cytokines TNFα, and IFNγ, the microvasculature produces tissue factor, ICAM, and VCAM to promote thrombosis, inflammation and to induce vascular barrier breakdown. Therefore, niche regulation is of vital importance to maintain and/or regenerate lung alveolar structures and gas exchange.
Lung tissue engineering is aiming to build an “off-the-shelf” organ by decellularizing lung extracellular matrix scaffolds, and repopulating with cells to regenerate functional airways and vasculature. However, imperfect lung microvasculature cell phenotype and niche characteristics impair vascular barrier and gas exchange in engineered lungs. Regulation of culture regimens, including flow rates and patterns, vascular pressure, oxygen tension, and medium composition to mimic the in vivo physiological microenviroment, may improve formation of an entirely new lung microvasculature.
This Research Topics will welcome reviews and original research articles in, but not limited to, areas including i) the biological mechanisms of lung microvascular niche in disease; ii) niche regulation such as changes of flow (shear stress), cytokines, or cell delivery on microvascular function; iii) culture methods to improve vascularization for de nove engineered lung microvasculature.


Keywords: shear stress, oxygen tension, cell therapy, gene therapy, extracellular matrix, lung tissue engineering, vascular homeostasis


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