Nadim Srour1, Bernard Thébaud2. 1. 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. 2. 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.
Abstract
BACKGROUND AIMS: 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.
BACKGROUND AIMS: 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: Katsuyuki Takeda; Tracy L Webb; Fangkun Ning; Yoshiki Shiraishi; Daniel P Regan; Lyndah Chow; Mia J Smith; Shigeru Ashino; Amanda M Guth; Sophie Hopkins; Erwin W Gelfand; Steven Dow Journal: J Immunol Date: 2018-01-19 Impact factor: 5.422