Concise Review: Clinical Prospects for Treating Chronic Obstructive Pulmonary Disease with Regenerative Approaches

Stem Cells Translational Medicine







Chronic obstructive pulmonary disease (COPD) is becoming a major cause of death worldwide. COPD is characterized by a progressive and not fully reversible airflow limitation caused by chronic small airway disease and lung parenchymal destruction. Clinically available drugs improve airflow ob- struction and respiratory symptoms but cannot cure the disease. Slowing the progressive lung destruction or rebuilding the destroyed lung structure is a promising strategy to cure COPD. In contrast to small animal models, pharmacological lung regeneration is difficult in human COPD. Maturation, aging, and senescence in COPD lung cells, including endogenous stem cells, may affect the regenerative capacity following pharmacological therapy. The lung is a complex organ composed of more than 40 different cell types; therefore, detailed analyses, such as epigenetic modification analysis, in each specific cell type have not been performed in lungs with COPD. Recently, a method for the direct isolation of individual cell types from human lung has been developed, and fingerprints of each cell type in COPD lungs can be analyzed. Research using this technique combined with the recently discovered lung endogenous stem-progenitor populations will give a better understanding about the fate of COPD lung cells and provide a future for cell-based therapy to treat this intractable disease.



The challenges of lung regeneration have made clear what we know and what we do not know about lungs. The lack of knowl- edge about the role of lung endogenous stem cells and func- tional changes in lung cells in COPD limits the development of lung regenerative therapy. The recent discovery of several can- didates for lung endogenous stem cells [38, 39] and a new isola- tion technique for human lung cells [56] will give a better under- standing of the COPD lungs, and those fundamentally different approaches will open a new paradigm for future regenerative therapies for COPD patients.


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