Abstract
Human respiratory disease research currently lacks in vitro models that recapitulate most of the physiology and architecture of the lung. Furthermore, the complex composition and structure of the lung, as well as anatomical differences between humans and mice, frequently lead to disappointing results applied in vivo. Recent advances in organoid technology include new, sophisticated in vitro culture tools that have stimulated considerable interest due to their potential ability to functionally mimic the organ rather than two-dimensional culture or animal models. Hence, pluripotent stem cell-based organoid studies are emerging as an alternative approach able to recapitulate tissue architecture with remarkable fidelity. Moreover, these biomimetic tissue models can be used to investigate the mechanisms of progression of various diseases. Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are the most severe multifactorial respiratory disorders, characterized by irreversible airflow and progressive disease in elderly people. These diseases exhibit a progressive loss of alveolar type 2 epithelial (AT2) cells and accumulation of macrophages in the alveoli, leading to impaired pulmonary function. Despite recent advances in the study of COPD and IPF, effective treatments are lacking because our understanding of those diseases is hindered by their unknown mechanisms. Thus, in this review, the role of AT2 cells and macrophages is highlighted, along with their cell sources and applications for IPF and COPD modeling.
Highlights
The lung is a highly complex and dynamic organ
We found that the receptor for advanced glycan end products (RAGE) pathway was related with chronic obstructive pulmonary disease (COPD) pathology [49,50]
Cui et al [71] reported that apolipoprotein E, produced primarily by monocyte-derived alveolar macrophages, promoted type I collagen phagocytosis and j-organoid.org interacted with low-density lipoprotein receptor-related protein 1 leading to the resolution of lung fibrosis in Idiopathic pulmonary fibrosis (IPF) mice
Summary
The lung is a highly complex and dynamic organ. In its proximal part, the bronchiolar airways are connected to a single tracheal tube. IPF is a frequent and severe type of idiopathic interstitial pneumonia with an unknown etiology It is characterized by progressive worsening of dyspnea and declining pulmonary function, and it has a median survival of approximately 2 to 3 years after diagnosis. Both the prevalence and incidence of IPF have consistently increased in recent years; it is considered that severe exposure to particulate matter (PM), smoking, and j-organoid.org viral or bacterial respiratory infections may be risk factors for IPF [4]. Since COPD and IPF represent major causes of disease and death, there is a desperate need for new effective tools In this context, the role of alveolar type II epithelial (AT2) cells and macrophages as major cellular compartments will be discussed
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