Mesenchymal Stromal Cells in Animal Bleomycin Pulmonary Fibrosis Models: A Systematic Review.
Idiopathic pulmonary fibrosis is an inexorably progressive lung disease with few available treatments. New therapeutic options are needed. Stem cells have generated much enthusiasm for the treatment of several conditions, including lung diseases. Human trials of mesenchymal stromal cell (MSC) therapy for pulmonary fibrosis are under way. To shed light on the potential usefulness of MSCs for human disease, we aimed to systematically review the preclinical literature to determine if MSCs are beneficial in animal bleomycin pulmonary fibrosis models. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal bleomycin models of pulmonary fibrosis. Studies using embryonic stem cells or induced pluripotent stem cells were excluded. Seventeen studies were selected, all of which used MSCs in rodents. MSC therapy led to an improvement in bleomycin-induced lung collagen deposition in animal lungs and in the pulmonary fibrosis Ashcroft score in most studies. MSC therapy improved histopathology in almost all studies in which it was evaluated qualitatively. Furthermore, MSC therapy was found to improve 14-day survival in animals with bleomycin-induced pulmonary fibrosis. Bronchoalveolar lavage total and neutrophil counts, as well as transforming growth factor-β levels, were also reduced by MSCs. MSCs are beneficial in rodent bleomycin pulmonary fibrosis models. Since most studies examined the initial inflammatory phase rather than the chronic fibrotic phase, preclinical data offer better support for human trials of MSCs in acute exacerbations of pulmonary fibrosis rather than the chronic phase of the disease.


CONCLUSIONS
There has been increased interest in mesenchymal stromal cell therapy for lung diseases. A few small clinical trials are under way in idiopathic pulmonary fibrosis. Preclinical evidence was assessed in a systematic review, as is often done for clinical studies. The existing studies offer better support for efficacy in the initial inflammatory phase rather than the fibrotic phase that human trials are targeting.
Division of Pulmonology, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada Division of Pulmonology, Department of Medicine, Hôpital Charles-LeMoyne, Montreal, Quebec, Canada Department of Medicine, McGill University, Montreal, Quebec, Canada Mount Sinai Hospital Centre, Montreal, Quebec, Canada Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada nadim.srour@usherbrooke.ca.
Nadim
N
Srour
Regenerative Medicine Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada.
Bernard
B
Thébaud
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D001761:Bleomycin
Animal studies; Idiopathic pulmonary fibrosis; Stem cells; Systematic review; Therapy