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Translating Basic Research Into Clinical Practice |

Bronchopulmonary Dysplasia – Where have all the Stem Cells gone? Origin and (potential) function of resident lung stem cells

Marius Alexander Möbius, MD; Bernard Thébaud, MD, PhD
Author and Funding Information

The authors have nothing to disclose

1Department of Neonatology and Pediatric Critical Care Medicine, Medical Faculty, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany


2DFG Research Center and Cluster of Excellence for Regenerative Therapies (CRTD), Technische Universität Dresden, Dresden, Germany


3Regenerative Medicine Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada

4Division of Neonatology, Department of Pediatrics, Children’s Hospital of Eastern Ontario (CHEO) and CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada

5Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada

Correspondence to: Bernard Thébaud Ottawa Hospital Research Institute Sinclair Centre for Regenerative Medicine 501 Smyth Rd Ottawa, ON K1H 8L6 Canada.


Copyright 2017, . All Rights Reserved.


Chest. 2017. doi:10.1016/j.chest.2017.04.173
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Abstract

Celebrating its 50th anniversary in 2017, bronchopulmonary dysplasia (BPD) - the chronic lung disease of prematurity that follows ventilator and O2 therapy for acute respiratory failure - remains the most frequent complication of extreme prematurity. Survival of premature infants born at increasingly earlier stages of gestation has made the prevention of lung injury increasingly challenging. BPD is postulated to be a misdirection of many functions in the developing lung including growth factor signalling and matrix as well as cellular composition, resulting in impaired alveolar and lung vascular growth. Despite improvements in understanding the mechanisms that regulate normal lung development, BPD remains without therapies. Recent insights into stem cell biology have identified the repair potential of stem cells. Promising preclinical studies demonstrated the lung protective effects of stem cell-based therapies in animal models mimicking BPD, leading to early phase clinical trials. While the time is ripe to conduct well-designed early phase clinical trials, much more needs to be learned about the biology of these cells in order to develop safe, efficient, high quality, clinical-grade cell products. Stem cells are essential for normal organ development, maintenance and repair. It is therefore biologically plausible that exhaustion/dysfunction of resident lung stem cells contributes to the inability of the immature lung to repair itself. Understanding how normal lung stem cells function and how these cells are perturbed in BPD may prove useful in designing superior cell products with enhanced repair capabilities to ensure the successful translation of basic research into clinical practice.


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