Tatiana Maron-Gutierrez1, John G Laffey, Paolo Pelosi, Patricia R M Rocco. 1. aLaboratory of Immunopharmacology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil bDepartment of Anesthesia, Keenan Research Centre for Biomedical Science, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada cDepartment of Surgical Sciences and Integrated Diagnostics, University of Genoa dIRCCS San Martino IST, Genoa, Italy eLaboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Abstract
PURPOSE OF REVIEW: Acute respiratory distress syndrome (ARDS) is a multifaceted lung disease with no current effective therapy. Many clinical trials using conventional pharmacologic therapies have failed, suggesting the need to examine alternative approaches. Thus, attention has focused on the therapeutic potential of cell-based therapies for ARDS, with promising results demonstrated in relevant preclinical disease models. We review data concerning the therapeutic promise of cell-based therapies for ARDS. RECENT FINDINGS: Recent experimental studies provide further evidence for the potential of cell-based therapies in ARDS. A number of cell types, particularly mesenchymal stem/stromal cells (MSCs), bone marrow-derived mononuclear cells, endothelial progenitor cells, and embryonic stem cells have been demonstrated to reduce mortality and modulate the inflammatory and remodeling processes in relevant preclinical ARDS models. Multiple insights have emerged in regard to the mechanisms by which cell therapies - particularly MSCs - exert their effects, with evidence supporting direct cell-mediated and paracrine-mediated mechanisms of action. Diverse paracrine mechanisms exist, including the release of cytokines, growth factors (such as keratinocyte growth factor), and antimicrobial peptides, and transfer of cellular contents such as peptides, nucleic acids, and mitochondria via either microvesicular or direct cell-cell contact-mediated transfer. SUMMARY: Cell-based therapies offer considerable promise for the treatment of ARDS. While MSC-based therapies are being rapidly advanced toward clinical testing, clear therapeutic potential exists for other cell types for ARDS. A greater understanding of current knowledge gaps should further enhance the therapeutic potential of cell-based therapies for ARDS.
PURPOSE OF REVIEW: Acute respiratory distress syndrome (ARDS) is a multifaceted lung disease with no current effective therapy. Many clinical trials using conventional pharmacologic therapies have failed, suggesting the need to examine alternative approaches. Thus, attention has focused on the therapeutic potential of cell-based therapies for ARDS, with promising results demonstrated in relevant preclinical disease models. We review data concerning the therapeutic promise of cell-based therapies for ARDS. RECENT FINDINGS: Recent experimental studies provide further evidence for the potential of cell-based therapies in ARDS. A number of cell types, particularly mesenchymal stem/stromal cells (MSCs), bone marrow-derived mononuclear cells, endothelial progenitor cells, and embryonic stem cells have been demonstrated to reduce mortality and modulate the inflammatory and remodeling processes in relevant preclinical ARDS models. Multiple insights have emerged in regard to the mechanisms by which cell therapies - particularly MSCs - exert their effects, with evidence supporting direct cell-mediated and paracrine-mediated mechanisms of action. Diverse paracrine mechanisms exist, including the release of cytokines, growth factors (such as keratinocyte growth factor), and antimicrobial peptides, and transfer of cellular contents such as peptides, nucleic acids, and mitochondria via either microvesicular or direct cell-cell contact-mediated transfer. SUMMARY: Cell-based therapies offer considerable promise for the treatment of ARDS. While MSC-based therapies are being rapidly advanced toward clinical testing, clear therapeutic potential exists for other cell types for ARDS. A greater understanding of current knowledge gaps should further enhance the therapeutic potential of cell-based therapies for ARDS.
Authors: Shibani Pati; Marcello Pilia; Juanita M Grimsley; Alexia T Karanikas; Blessing Oyeniyi; John B Holcomb; Andrew P Cap; Todd E Rasmussen Journal: Shock Date: 2015-12 Impact factor: 3.454