![]() Stem cells are able to repair injured airways and lungs by modulating multiple biological processes of the immune response, alveolar fluid clearance, cell fate, and drug delivery through paracrine and autocrine mechanisms, predominantly via extracellular vesicles ( i.e., exosomes). For example, mesenchymal stromal stem cells (MSCs) derived from the umbilical cord blood, bone marrow, adipose, placenta, and other tissues are tested by registered clinical trials. Rapidly accumulating evidence in preclinical models suggests that cell-based therapy may be a promising therapeutic strategy for lung injury repair. Amidst the list, COPD is the third leading cause of global fatality. Acute and chronic lung diseases, including coronavirus disease 2019 (COVID-19), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), bronchopulmonary dysplasia (BPD), pulmonary arterial hypertension (PAH), silicosis, sarcoidosis, extensively drug-resistant tuberculosis, chronic obstructive pulmonary diseases (COPD), and idiopathic pulmonary fibrosis (IPF), have high morbidity and mortality. ![]() Respiratory diseases are a top-ranked cause of death toll worldwide. The future directions for both new clinical trials and preclinical studies are discussed. In this review, we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials. Five routes and a series of doses have been tested for tolerance and advantages of different regimes. To date, the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD, acute respiratory distress syndrome, bronchial dysplasia, idiopathic pulmonary fibrosis, pulmonary artery hypertension, and silicosis. Mesenchymal stromal cells, endothelial progenitor cells, peripheral blood stem cells, and lung progenitor cells have been applied to clinical trials. Stem cells consist of totipotent, pluripotent, multipotent, and unipotent cells with the potential to differentiate into cell types requested for repair. Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses, as proved by accumulating preclinical studies. There are no effective and curative treatments, but supportive care only. Respiratory diseases, including coronavirus disease 2019 and chronic obstructive pulmonary disease (COPD), are leading causes of global fatality.
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