title: Stem cells in animal asthma models: a systematic review.
abstract: OBJECTIVE
  Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted.
  
  
  METHODS
  The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models.
  
  
  RESULTS
  Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness.
  
  
  CONCLUSIONS
  Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials.
authors.affiliation: Université de Sherbrooke, Faculté de Médecine et des Sciences de la Santé, Department of Medicine, Division of Pulmonology, Sherbrooke, Canada; Hôpital Charles-LeMoyne, Department of Medicine, Division of Pulmonology, Montreal, Canada; McGill University, Department of Medicine, Montreal, Canada; Mount Sinai Hospital Centre, Montreal, Canada; The Ottawa Hospital Research Institute, Clinical Epidemiology Program, Ottawa, Canada. Electronic address: nadim.srour@usherbrooke.ca.
authors.forename: Nadim
authors.initials: N
authors.lastname: Srour
authors.affiliation: The Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Canada; Children's Hospital of Eastern Ontario, Ottawa, Canada; The University of Ottawa, Faculty of Medicine, Ottawa, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thébaud
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D016239:MEDLINE; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: C508598:IL4 protein, human; C508599:IL5 protein, human; D015848:Interleukin-5; D015847:Interleukin-4
keywords: animal studies; asthma; stem cells; systematic review; therapy