Reconstituting Mouse Lungs with Conditionally Reprogrammed Human Bronchial Epithelial Cells

Ryan Laranger, Jennifer R. Peters-Hall, Melissa Coquelin, Busola R. Alabi, Christopher T. Chen, Woodring E. Wright, Jerry W. Shay

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We developed methods for conditionally reprogramming (CR) primary human bronchial epithelial cells (HBECs) to extend their functional lifespan and permit their differentiation into both upper and lower airway lung epithelium. We also developed a bioreactor to support vascular perfusion and rhythmic breathing of decellularized mouse lungs reconstituted with CR HBECs isolated from patients with and without cystic fibrosis (CF). While conditionally reprogrammed cells only differentiate into an upper airway epithelium after 35 days at the air-liquid interface, in reconstituted lungs these cells differentiate into upper airway bronchial epithelium and lower airway alveolar structures after 12 days. Rapid scale-up and the ability to obtain clonal derivatives of primary patient-derived HBECs without the need for genetic manipulation may permit rapid reconstitution of the lung epithelium; facilitating the study of lung disease in tissue-engineered models.

Original languageEnglish (US)
Pages (from-to)559-568
Number of pages10
JournalTissue Engineering - Part A
Volume24
Issue number7-8
DOIs
StatePublished - Apr 2018

Keywords

  • Cystic fibrosis
  • Decellularized lung
  • Multipotent
  • ROCK inhibitor
  • Tissue engineering

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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  • Cite this

    Laranger, R., Peters-Hall, J. R., Coquelin, M., Alabi, B. R., Chen, C. T., Wright, W. E., & Shay, J. W. (2018). Reconstituting Mouse Lungs with Conditionally Reprogrammed Human Bronchial Epithelial Cells. Tissue Engineering - Part A, 24(7-8), 559-568. https://doi.org/10.1089/ten.tea.2017.0114