Extracellular matrix in lung development, homeostasis and disease

Abstract

The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.

Second-generation lung-on-a-chip array with a stretchable biological membrane

“…The main drawback of PDMS is that it is synthetic which limits its function and the ability to mimic physiological capacities. The ECM of the lung alveolar region has structural and mechanical cell substrate functions but beyond that the ECM is pivotal in determining normal cellular function and differentiation in health and dysregulation in disease 12,29,30 . Another limitation of PDMS membranes is the absorption and adsorption of small molecules and the effect on the ECM as local reservoir of growth factors and bioactive molecules, which are not maintained by the microenvironment at physiological concentrations, and therefore distort effects in the system.…”

“…Although PDMS has good elastic, optical and biocompatible properties, it can distort the biochemical microenvironment through high adsorption and absorption levels of small molecules 11 . In addition, the nonbiological PDMS differs in important ways from the molecular composition and intrinsic stiffness of the native extracellular matrix (ECM), which is known to affect cellular phenotype and homeostasis 12,13 . A complex ECM environment provides the structural basis for cellular growth, and influences cellular morphology, functionality, differentiation and other traits 14,15 .…”

Limitations of recellularized biological scaffolds for human transplantation

“…One of the major advantages of acellular natural scaffolds is that they should retain the native ECM composition, topography, and biomechanics that is known to be organ specific (Petersen et al, 2010;Shojaie et al, 2015;Tschumperlin, 2015;Weber, Annenberg, Wright, Braverman, & Mesh, 2014;Zhou et al, 2018). ECM is essential for cell attachment, proliferation, differentiation, and therefore, regeneration (Lawson et al, 2016;Mih, Marinkovic, Liu, Sharif, & Tschumperlin, 2012;Petersen et al, 2010;Susek et al, 2018).…”

Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche

“…The core proteins of the lung include type IV collagen, laminin, fibronectin, heparan sulfate proteoglycan (HSPG or perlecan), and chondroitin sulfate proteoglycan (CSPG) that form a mesh-like structure. ECM-associated proteins include nidogen/entactin, hyaluronate, tenascin X and C, thrombospondin, and agrin (Kalluri, 2003;Balestrini and Niklason, 2015;Zhou Y. et al, 2018). These components are interconnected to allow selective transfer of cells and signaling molecules, regulating tissue development, homeostasis, and disease pathogenesis (Bottaro et al, 2002;Vorotnikova et al, 2010;Otranto et al, 2012).…”

“…Two characteristics of the ACM that are fundamental for bioengineering of all organs are the matrix topography and stiffness (Zhou Y. et al, 2018). Matrix topography includes the organization, size, and geometry of the matrix that translates specific signals to the cells mediating their shape, morphology, and function at the micro-and nanoscale (Bettinger et al, 2009).…”