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Tissue Eng Part A. 2018 Apr;24(7-8):559-568. doi: 10.1089/ten.TEA.2017.0114. Epub 2017 Sep 25.

Reconstituting Mouse Lungs with Conditionally Reprogrammed Human Bronchial Epithelial Cells.

Author information

1
1 Department of Cell Biology, University of Texas Southwestern Medical Center , Dallas, Texas.
2
2 Biomedical Engineering Program, University of Texas Southwestern Medical Center , Dallas, Texas.

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.

KEYWORDS:

ROCK inhibitor; cystic fibrosis; decellularized lung; multipotent; tissue engineering

PMID:
28726588
PMCID:
PMC5905853
[Available on 2019-04-01]
DOI:
10.1089/ten.TEA.2017.0114
[Indexed for MEDLINE]

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