Novel Stem/Progenitor Cell Population from Murine Tracheal Submucosal Gland Ducts with Multipotent Regenerative Potential

Author:

Hegab Ahmed E.1,Ha Vi Luan1,Gilbert Jennifer L.1,Zhang Kelvin Xi2,Malkoski Stephen P.3,Chon Andy T.1,Darmawan Daphne O.1,Bisht Bharti1,Ooi Aik T.1,Pellegrini Matteo4,Nickerson Derek W.1,Gomperts Brigitte N.1567

Affiliation:

1. Department of Pediatrics, David Geffen School of Medicine at University of California Los Angeles, University of California Los Angeles School of Medicine, Los Angeles, California, USA

2. Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA

3. Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver Health Sciences Center, Aurora, Colorado, USA

4. Department of Molecular, Cellular, and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA

5. Jonsson Comprehensive Cancer Center, Los Angeles, California, USA

6. Department of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA

7. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, California, USA

Abstract

Abstract The airway epithelium is in direct contact with the environment and therefore constantly at risk for injury. Basal cells (BCs) have been found to repair the surface epithelium (SE), but the contribution of other stem cell populations to airway epithelial repair has not been identified. We demonstrated that airway submucosal gland (SMG) duct cells, in addition to BCs, survived severe hypoxic-ischemic injury. We developed a method to isolate duct cells from the airway. In vitro and in vivo models were used to compare the self-renewal and differentiation potential of duct cells and BCs. We found that only duct cells were capable of regenerating SMG tubules and ducts, as well as the SE overlying the SMGs. SMG duct cells are therefore a multipotent stem cell for airway epithelial repair This is of importance to the field of lung regeneration as determining the repairing cell populations could lead to the identification of novel therapeutic targets and cell-based therapies for patients with airway diseases.

Funder

CIRM

American Thoracic Society/Chronic Obstructive Pulmonary Disease Foundation

The Concern Foundation

The UCLA Jonsson Comprehensive Cancer Center Thoracic Oncology Program/Lung Cancer specialized program of research excellence

the University of California Cancer Research Coordinating Committee

Gwynne Hazen Cherry Memorial Laboratories

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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