Journal article
Culture Conditions Differentially Regulate the Inflammatory Niche and Cellular Phenotype of Tracheo-Bronchial Basal Stem Cells
American journal of physiology. Lung cellular and molecular physiology, Vol.328(4), pp.L538-L553
04/01/2025
DOI: 10.1152/ajplung.00293.2024
PMCID: PMC12261264
PMID: 39982813
Abstract
Bronchial epithelial cells derived from the tracheo-bronchial regions of human airways (HBECs) provide a valuable
model for studying pathological mechanisms and evaluating therapeutics. This cell population comprises a mixed population of basal cells (BCs), the predominant stem cell in airways capable of both self-renewal and functional differentiation. Despite their potential for regenerative medicine, BCs exhibit significant phenotypic variability in culture. To investigate how culture conditions influence BC phenotype and function, we expanded three independent BC isolates in three media: airway epithelial cell growth medium (AECGM), dual-SMAD inhibitor (DSI)-enriched AECGM, and Pneumacult Ex plus (PEx+). Analysis through RNA sequencing, immune assays and impedance measurements revealed that PEx+ media significantly drove cell proliferation and a broad pro-inflammatory phenotype in BCs. In contrast, BCs expanded in AECGM, displayed increased expression of structural and extracellular matrix components at higher passage. AECGM increased expression of some cytokines at high passage, while DSI suppressed inflammation implicating the involvement TGF-β in BC inflammatory processes. Differentiation capacity of BCs declined with time in culture irrespective of expansion media. This was associated with an increase in PLUNC expressing secretory cells in AECGM and PEx+ media consistent with the known immune modulatory role of PLUNC in the airways. These findings highlight the profound impact of media conditions on inflammatory niche established by, and function of,
expanded BCs. The broad pro-inflammatory phenotype driven by PEx+ media, in particular, should be considered in the development of cell-based models for airway diseases and therapeutic application.
Details
- Title: Subtitle
- Culture Conditions Differentially Regulate the Inflammatory Niche and Cellular Phenotype of Tracheo-Bronchial Basal Stem Cells
- Creators
- Shubha Murthy - University of IowaDenise A Seabold - University of IowaLalit K Gautam - University of IowaAdrian M Caceres - University of IowaRosemary Sease - University of Southern CaliforniaBen A Calvert - University of IowaShana M Busch - University of Southern CaliforniaAaron Neely - City Of Hope National Medical CenterCrystal N Marconett - University of Southern CaliforniaAmy L Ryan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.328(4), pp.L538-L553
- DOI
- 10.1152/ajplung.00293.2024
- PMID
- 39982813
- PMCID
- PMC12261264
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1522-1504
- eISSN
- 1522-1504
- Publisher
- AMER PHYSIOLOGICAL SOC
- Grant note
- R01HL139828 / HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) RYAN21XX0 / Cystic Fibrosis Foundation (CFF) FIRTH17XX0 / Cystic Fibrosis Foundation (CFF)
- Language
- English
- Electronic publication date
- 02/21/2025
- Date published
- 04/01/2025
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984792367002771
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