title: Preclinical evaluation of cell-based strategies to prevent or treat bronchopulmonary dysplasia in animal models: a systematic review.
abstract: Bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity as no effective treatment is available to date. This calls for the exploration of new therapeutic options like cell therapy, which is already effective for various human (lung) disorders. We systematically searched the MEDLINE, Embase, and Web of Science databases from the earliest date till January 2017 and included original studies on the perinatal use of cell-based therapies (i.e. cells and/or cell-derivatives) to treat BDP in animal models. Fourth publications describing 47 interventions were retrieved. Newborn mice/rats raised in a hyperoxic environment were studied in most interventions. Different cell types - either intact cells or their conditioned medium - were administered, but bone marrow and umbilical cord blood derived mesenchymal stem cells were most prevalent. All studies reported positive effects on outcome parameters including alveolar and vascular morphometry, lung function, and inflammation. Cell homing to the lungs was demonstrated in some studies, but the therapeutic effects seemed to be mostly mediated via paracrine modulation of inflammation, fibrosis and angiogenesis.
  
  
  CONCLUSIONS
  Multiple rat/mouse studies show promise for cell therapy for BPD. Yet careful study of action mechanisms and side effects in large animal models is imperative before clinical translation can be achieved.
authors.affiliation: a Department of Development and Regeneration, Group Biomedical Sciences , KU Leuven , Leuven , Belgium.
authors.forename: Flore
authors.identifier: http://orcid.org/0000-0001-8578-9650
authors.initials: F
authors.lastname: Lesage
authors.affiliation: a Department of Development and Regeneration, Group Biomedical Sciences , KU Leuven , Leuven , Belgium.|b Department of Obstetrics and Gynaecology , Clínica Alemana Universidad del Desarrollo , Santiago , Chile.
authors.forename: Julio
authors.identifier: http://orcid.org/0000-0001-6260-2814
authors.initials: J
authors.lastname: Jimenez
authors.affiliation: a Department of Development and Regeneration, Group Biomedical Sciences , KU Leuven , Leuven , Belgium.|c Department of Pediatrics , University Hospitals Leuven , Leuven , Belgium.
authors.forename: Jaan
authors.identifier: http://orcid.org/0000-0001-9339-5408
authors.initials: J
authors.lastname: Toelen
authors.affiliation: a Department of Development and Regeneration, Group Biomedical Sciences , KU Leuven , Leuven , Belgium.|d Research Department of Maternal Fetal Medicine , UCL Institute for Women's Health (IWH), University College London , London , United Kingdom.
authors.forename: Jan
authors.identifier: http://orcid.org/0000-0002-4920-945X
authors.initials: J
authors.lastname: Deprest
mesh_terms: D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control / Q000628:therapy*; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D051381:Rats; D016896:Treatment Outcome
chemical_list: D017077:Culture Media, Conditioned
keywords: Bronchopulmonary dysplasia; animal models; cell therapy; chronic lung disease; conditioned medium; mesenchymal stem cells