Concise review: clinical prospects for treating chronic obstructive pulmonary disease with regenerative approaches

Abstract

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 obstruction 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.

Figure 1.

Structural changes and pathogenesis of COPD. (A): Alveolar structure in normal lung and COPD lung. The lung is composed of millions of alveoli surrounded by a capillary network. Alveolar destruction and small airway obstruction are seen in COPD lung. (B): Mechanisms of airflow limitation in COPD. Insufficient repair capacity of lung endogenous stem cells may cause the alveolar destruction. Abbreviations: COPD, chronic obstructive pulmonary disease; CT, computed tomography.

Figure 2.

Conceptual model of new alveolarization. The presence of key proteins in the extracellular matrix is required for lung regeneration. Elastic fibers made by extracellular matrices, such as elastin, surround alveoli. These fibers support the alveolar septation.