Targeting the lung endothelial niche to promote angiogenesis and regeneration: A review of applications

Abstract

Lung endothelial cells comprise the pulmonary vascular bed and account for the majority of cells in the lungs. Beyond their role in gas exchange, lung ECs form a specialized microenvironment, or niche, with important roles in health and disease. In early development, progenitor ECs direct alveolar development through angiogenesis. Following birth, lung ECs are thought to maintain their regenerative capacity despite the aging process. As such, harnessing the power of the EC niche, specifically to promote angiogenesis and alveolar regeneration has potential clinical applications. Here, we focus on translational research with applications related to developmental lung diseases including pulmonary hypoplasia and bronchopulmonary dysplasia. An overview of studies examining the role of ECs in lung regeneration following acute lung injury is also provided. These diseases are all characterized by significant morbidity and mortality with limited existing therapeutics, affecting both young children and adults.

Roles of Macrophages and Endothelial Cells and Their Crosstalk in Acute Lung Injury

“…Additionally, they are active participants in the immune response, aiding in the recruitment of immune cells to sites of infection or inflammation within the lung [ 9 , 89 , 90 ]. ECs also contribute to the management of the body’s inflammatory responses, playing a crucial role in maintaining pulmonary homeostasis [ 79 , 91 ].…”

“…The recovery and resolution of ALI and ARDS heavily depend on the processes of endothelial regeneration and vascular repair [ 9 , 11 , 91 , 103 ]. Following an initial insult that damages ECs, these cells initiate a complex process aimed at regenerating and repairing the lung’s blood vessels, with the primary objective of restoring their integrity and functionality [ 7 , 12 , 85 , 95 ].…”

Impact of different tissue dissociation protocols on endothelial cell recovery from developing mouse lungs

“…Lung endothelial cells also play a pivotal role in lung homeostasis [8] and the development and progression of a spectrum of adult lung diseases [9], including the sexual dimorphism noted in lung disease [10, 11]. Thus, exploitation of the lung endothelial niche is seen as a potential avenue for promoting the regeneration of diseased lungs [12]. For these reasons, there is tremendous scope for the application of flow cytometry and fluorescence‐activated cell sorting (FACS) in studies on endothelial cell function in lung development, homeostasis, and disease.…”

The lung mesenchyme in development, regeneration, and fibrosis

“…This is mainly due to a gap in our knowledge regarding mesenchymal cell heterogeneity and hierarchy, particularly in terms of cellular identity and plasticity, and how this translates to adaptive versus maladaptive tissue repair in physiological and pathophysiological settings, respectively. In this Review, we will focus our discussion on mesenchymal cell functions in support of epithelial repair/ regeneration, and refer readers interested in a more expanded understanding of endothelial cell regeneration and vascular repair, the role of angiocrine-derived factors in epithelial regeneration, and mesenchymal-endothelial interactions to other recently published reviews as well as original research articles (1)(2)(3)(4)(5)(6).…”