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Publications

Journal Article Ppublish 9 citations

PubMed: 40226365 DOI: 10.1016/j.celbio.2025.100013

Development of a 3D bioengineered human lung submucosal gland ductal airway model to study mucociliary clearance .

Cell Biomater 1(2)

Authors: Hoyeol Kim, Sujung Yi, Pramodha Liyanage, Shuyang Zhao, Kathryn A Wikenheiser-Brokamp, Lisa McMillin, Yan Xu, Joseph A Kitzmiller, Jeffrey A Whitsett, Anjaparavanda P Naren, Kyu Shik Mun

Affiliations

  • Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
  • Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
  • Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
  • Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
  • Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Lead Contact.

Abstract

Mucociliary clearance (MCC) is critical in maintaining lung health and preventing respiratory infections. MCC is impaired in people with cystic fibrosis, due to accumulation of thick, sticky mucus resulting from defective cystic fibrosis transmembrane conductance regulator channel function. In this study, we developed a unique 3D lung submucosal gland ductal airway model utilizing primary human submucosal gland epithelial cells, which enables the formation of physiologically relevant architecture of the ductal epithelium including ciliary cells within a 3D bioprinted scaffold. Our observation demonstrates that this model not only enables the fabrication of human lung submucosal gland ductal airway-like structure mimicking physiology, also facilitates quantitative measurement of patient-specific MCC and determines pharmacological effects. Our results suggest that this model could be a valuable tool for understanding mechanisms underlying impaired MCC and testing the efficacy of novel therapeutic strategies for the treatment of respiratory diseases such as cystic fibrosis.

MeSH

Cells, Research Design, Lung, Fibrosis, Mucociliary Clearance, Cystic Fibrosis, Therapeutics