Generation of Region-Specific Airway Basal Cells

Airway basal cells are essential for the homeostatic maintenance and repair of the respiratory epithelium. Recent study also revealed pronounced regional differences between human proximal and distal airway cell types, including basal cells. UTHealth researchers and their collaborators established a novel strategy to generate region-specific proximal, intermediate, and distal airway basal cells derived from human induced pluripotent stem cells (hiPSCs), leading to new opportunities in regeneration medicine, cell-based therapies, and related disease research.

Background

Basal cells are tissue-specific adult multipotent stem cells of various organs, including skin, esophagus, olfactory, and the airway epithelia. Because airway basal cells self-renew and generate all specialized airway lineages, they hold long-term therapeutic promise for both environmental and genetic airway diseases that affect basal and other airway lineages. They are also well suited for modeling disease mechanisms – including environmentally driven conditions such as chronic obstructive pulmonary disease (COPD) and lung squamous cell carcinoma, as well as inherited disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia (PCD).

Significance and Impact

Traditionally, basal cells were considered to be homogenous until recent studies revealed key evidence for basal cell heterogeneity in the airways of the lung. These differences include variations in lineage abundance, molecular phenotypes, and functions of each cell type in both homeostasis and repair. UTHealth researchers and their collaborator at MDACC established a new strategy to generate region-specific proximal, intermediate, and distal airway basal cells from hiPSCs. The availability of human iPSC-derived region-specific airway basal stem cells opens up significant opportunities for broad applications in regenerative medicine, lung development studies, and airway disease research.

Benefits/Technology Advantages

• hiPSC-derived region-specific proximal, intermediate, and distal airway basal cells exhibit molecular signatures and phenotypes resembling their counterparts in human large, medium, and small airways.

• Functional characterization of generated proximal airway basal cells demonstrated robust differentiation potential in vitro and in vivo.

Intellectual Property Status

Provisional patent application filed.

Available for licensing.

Selected Publications

Related publications in preparation.

About the Inventors