Unlocking the Future: Pluripotent Stem Cell-Based Lung Repair

Abstract

The human respiratory system is susceptible to a variety of diseases, ranging from chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis to acute respiratory distress syndrome (ARDS). Today, lung diseases represent one of the major challenges to the health care sector and represent one of the leading causes of death worldwide. Current treatment options often focus on managing symptoms rather than addressing the underlying cause of the disease. The limitations of conventional therapies highlight the urgent clinical need for innovative solutions capable of repairing damaged lung tissue at a fundamental level. Pluripotent stem cell technologies have now reached clinical maturity and hold immense potential to revolutionize the landscape of lung repair and regenerative medicine. Meanwhile, human embryonic (HESCs) and human-induced pluripotent stem cells (hiPSCs) can be coaxed to differentiate into lung-specific cell types such as bronchial and alveolar epithelial cells, or pulmonary endothelial cells. This holds the promise of regenerating damaged lung tissue and restoring normal respiratory function. While methods for targeted genetic engineering of hPSCs and lung cell differentiation have substantially advanced, the required GMP-grade clinical-scale production technologies as well as the development of suitable preclinical animal models and cell application strategies are less advanced. This review provides an overview of current perspectives on PSC-based therapies for lung repair, explores key advances, and envisions future directions in this dynamic field.

Keywords: cell therapy; differentiation; hiPSC; lung; pluripotent stem cells; pulmonary; respiratory.

Figure 1

Current protocols for respiratory in vitro differentiation of hPSCs. Abbreviations:; ALI, air liquid interface; CK, CHIR (CHIR99021, GSK-3 Inhibitor/Wnt Activator +keratinocyte growth factor (KGF); CPM, carboxypeptidase M; DCI, dexamethasone, 3′,5′-cyclic adenosine monophosphate (cAMP), and 3-isobutyl-1-methylxanthine (IBMX); IWP2 (Wnt/ß-catenin inhibitor); LATS-IN-1 (Lat1/2 kinases Inhibitor); SACGM, small airway epithelial cell growth medium; SB431542 (TGFß-R Inhibitor); Y27632 (ROCK-Inhibitor).