Role of Mesenchymal Stem Cells and Extracellular Vesicles in Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic disease that leads to disability and death within 5 years of diagnosis. Pulmonary fibrosis is a disease with a multifactorial etiology. The concept of aberrant regeneration of the pulmonary epithelium reveals the pathogenesis of IPF, according to which repeated damage and death of alveolar epithelial cells is the main mechanism leading to the development of progressive IPF. Cell death provokes the migration, proliferation and activation of fibroblasts, which overproduce extracellular matrix, resulting in fibrotic deformity of the lung tissue. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising therapies for pulmonary fibrosis. MSCs, and EVs derived from MSCs, modulate the activity of immune cells, inhibit the expression of profibrotic genes, reduce collagen deposition and promote the repair of damaged lung tissue. This review considers the molecular mechanisms of the development of IPF and the multifaceted role of MSCs in the therapy of IPF. Currently, EVs-MSCs are regarded as a promising cell-free therapy tool, so in this review we discuss the results available to date of the use of EVs-MSCs for lung tissue repair.

Immune Mechanisms of Pulmonary Fibrosis with Bleomycin

“…MSCs are pluripotent stem cells that can differentiate into a variety of cell types, including bone cells (osteoblasts), cartilage cells (chondrocytes), muscle cells (myocytes), and adipocytes, which give rise to bone marrow adipose tissue (fat cells). In addition, MSCs in the stromal and perivascular areas near fibroblasts can regulate myofibroblast activity [ 267 ]. These results indicate that MSCs are effective for the treatment of BLM-induced fibrotic lung lesions in animals.…”

Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks

“…14 The origins of these myofibroblasts are multifaceted and are shown to be derived from epithelial cells, fibroblasts, fibrocytes, and endothelial cells. 15 Consequently, it leads to the formation of fibroblastic foci (predominant sites marked by an increase in the number of myofibroblasts), causing lung destruction/ distortion. These are considered the primary motivators of fibrotic disease, acting as a source of collagen-rich ECM, thereby serving as a major histopathological hallmark of IPF disease.…”

“…At the same time, their activated version, myofibroblasts, drives and synchronizes disproportionate ECM production in IPF . The origins of these myofibroblasts are multifaceted and are shown to be derived from epithelial cells, fibroblasts, fibrocytes, and endothelial cells . Consequently, it leads to the formation of fibroblastic foci (predominant sites marked by an increase in the number of myofibroblasts), causing lung destruction/distortion.…”

Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway

“…An emerging therapeutic approach for the treatment of pneumonia involves the use of exosomes derived from mesenchymal stem cells (MSCs). These exosomes have gained attention due to their potential to effectively reverse the symptoms of pneumonia [ 11 , 12 , 13 ], lung injury [ 14 , 15 ], acute respiratory distress syndrome (ARDS) [ 16 ], chronic obstructive pulmonary disease (COPD) [ 17 ], bronchial asthma [ 18 ], and idiopathic pulmonary fibrosis [ 19 ]. Exosomes are small extracellular vesicles (EVs) that contain various bioactive molecules, including proteins, lipids, and nucleic acids.…”