Diagnostic and Therapeutic Applications of Extracellular Vesicles in Interstitial Lung Diseases

Abstract

Interstitial lung diseases (ILDs) are chronic irreversible pulmonary conditions with significant morbidity and mortality. Diagnostic approaches to ILDs are complex and multifactorial. Effective therapeutic interventions are continuously investigated and explored with substantial progress, thanks to advances in basic understanding and translational efforts. Extracellular vesicles (EVs) offer a new paradigm in diagnosis and treatment. This leads to two significant implications: new disease biomarker discovery that enables reliable diagnosis and disease assessment and the development of regenerative medicine therapeutics that target fibroproliferative processes in diseased lung tissue. In this review, we discuss the current understanding of the role of diseased tissue-derived EVs in the development of interstitial lung diseases, the utility of these EVs as diagnostic and prognostic tools, and the existing therapeutic utility of EVs. Furthermore, we review the potential therapeutic application of EVs derived from various cellular sources.

Hermansky-Pudlak Syndrome and Lung Disease: Pathogenesis and Therapeutics

“…Future research is required to evaluate emerging cellular and molecular mechanisms in the development of HPS-PF. Extracellular vesicles (EVs) released by alveolar epithelial cells, lung fibroblast and endothelial cells are indicated in the pathogenesis of IPF (Bagnato and Harari, 2015;Bartel et al, 2020;Ibrahim et al, 2021). They drive lung fibroproliferative processes through activation of pro-fibrotic signaling pathways such as TGF-β signaling, Wnt and cellular senescence (Schafer et al, 2017;Martin-Medina et al, 2018;Barnes et al, 2019;Chanda et al, 2019;Parimon et al, 2019;Reyfman et al, 2019;Adams et al, 2020).…”

Understanding exosomes: Part 2—Emerging leaders in regenerative medicine

“…Ongoing research has led to significant advancements in the development of effective treatment approaches including EVs which provides a novel approach in the field of diagnostics (biomarkers) and therapy. 857 ILDs may occur idiopathically as a result of exposure to biological, chemical, or small particles, or resulting from co-morbidities such as connective tissue or autoimmune illnesses. 858,859 Chronic, progressive, irreversible fibrosis with substantial morbidity and death is a hallmark of ILDs' natural course.…”

Role of extracellular vesicles in lung diseases

“…A couple of reviews have demonstrated that EVs also play an important role in driving pulmonary fibro-proliferation. [98][99][100][101] The review from Ibrahim et al [98] demonstrated that EVs drove and accelerated the development and progression of interstitial lung disease via the following three main signaling pathways: Wingless-N-type (Wnt)/ b-catenin pathway, TGF-b pathway, and cellular senescence. [32] Martin-Medina et al [102] reported that BALFderived EVs from patients with IPF were enriched with Wnt5A, a significant signaling mediator that activated fibroblast proliferation and collagen production in the pathogenesis of IPF.…”

“…A couple of reviews have demonstrated that EVs also play an important role in driving pulmonary fibro-prolifera-tion [98–101] . The review from Ibrahim et al [98] demonstrated that EVs drove and accelerated the development and progression of interstitial lung disease via the following three main signaling pathways: Wingless-N-type (Wnt)/ β-catenin pathway, TGF-β pathway, and cellular senes-cence [32] .…”