Extracellular vesicles in idiopathic pulmonary fibrosis: pathogenesis and therapeutics

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium. Therapeutic options for IPF remain limited as current therapies only function to decrease disease progression. Recently, extracellular vesicles (EVs), including exosomes and microvesicles, have been recognized as paracrine communicators through the component cargo. The population of cell-specific microRNAs and proteins present in EVs can regulate gene expressions of recipient cells, resulting in modulation of biological activities. EV cargoes reflect cell types and their physiological and pathological status of donor cells. Many current researches have highlighted the functions of EVs on the epithelial phenotype and fibroproliferative response in the pathogenesis of IPF. Furthermore, some native EVs could be used as a cell-free therapeutic approach for IPF as vehicles for drug delivery, given their intrinsic biocompatibility and specific target activity. EV-based therapies have been proposed as a new potential alternative to cell-based approaches. The advantage is that EVs, depending on their source, may be less immunogenic than their parental cells, likely due to a lower abundance of transmembrane proteins such as major histocompatibility complex (MHC) proteins on the surface. In the last decade, mesenchymal stem cell (MSC)-derived EVs have been rapidly developed as therapeutic products ready for clinical trials against various diseases. Considering EV functional complexity and heterogeneity, there is an urgent need to establish refined systemic standards for manufacturing processes and regulatory requirements of these medicines. This review highlights the EV-mediated cellular crosstalk involved in IPF pathogenesis and discusses the potential for EV-based therapeutics as a novel treatment modality for IPF.

The effect of bioactivity of airway epithelial cells using methacrylated gelatin scaffold loaded with exosomes derived from bone marrow mesenchymal stem cells

“…Studies have shown that exosomes can alleviate and resolve bleomycin‐induced fibrosis by reconstructing normal alveolar structure, reducing collagen accumulation and decreasing apoptosis. The mechanism may be that MSC‐Exos regulate the phenotype of monocytes to relieve pulmonary fibrosis 27 . Not coincidentally, Xu et al injected human umbilical MSC‐Exos into mice treated with intratracheal silica suspension and found a significant reduction in lung injury and improvement in lung inflammation and fibrosis due to a mechanism, by which umbilical MSC‐Exos reduced collagen deposition in mouse embryonic fibroblasts exposed to SiO 2 28 .…”

Roles of telocytes dominated cell–cell communication in fibroproliferative acute respiratory distress syndrome

“…While idiopathic pulmonary fibrosis (IPF) and fibroproliferative ARDS are distinct entities, the underlying pathobiology of these diseases almost certainly share similarities. 6 Extracellular matrix (ECM) abnormally deposits in multi-focus of the lung tissue, accompanied by epithelial and endothelial cell injury, alveolar structure and lung compliance damage, ultimately leading to respiratory failure and death in the pathological process of pulmonary fibrosis. 7 Same as ARDS, therapeutic options for pulmonary fibrosis are also limited as current therapies could only delay disease progression.…”

“…Moreover, therapeutic methods remain limited, as current treatment strategies can only delay the progression of the disease. While idiopathic pulmonary fibrosis (IPF) and fibroproliferative ARDS are distinct entities, the underlying pathobiology of these diseases almost certainly share similarities 6 . Extracellular matrix (ECM) abnormally deposits in multi‐focus of the lung tissue, accompanied by epithelial and endothelial cell injury, alveolar structure and lung compliance damage, ultimately leading to respiratory failure and death in the pathological process of pulmonary fibrosis 7 …”

Regulation of Extracellular Vesicle-Mediated Immune Responses against Antigen-Specific Presentation

“…Extracellular vesicles (EVs) are lipid bilayer structures secreted by living cells and are classified into either exosomes, microvesicles (MVs), or apoptotic bodies, based on the intracellular production mechanism and size ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , …”