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      Mesenchymal stem cell therapy for laryngotracheal stenosis: A systematic review of preclinical studies

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          Abstract

          Background

          Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways.

          Methods

          PubMed, EMBASE, Google Scholar and the Cochrane Library were systematically searched from January 1980–January 2017 with the purpose of identifying all studies addressing the effect of MSC therapy on the airway. We assessed effect on inflammation, fibrosis, and MSC as a component in tissue engineering for treating defects in the airway.

          Results

          We identified eleven studies (n = 256 animals) from eight countries evaluating the effect of MSCs as a regenerative therapy in the upper airways. The studies indicate that MSC therapy may lead to a more constructive inflammatory response as well as support tissue regeneration.

          Conclusion

          There may be a favorable effect of MSCs in inhibiting inflammation and as a component in tissue engineering. Given the heterogeneous nature of the included animal studies, any clear conclusion regarding the effect of tracheal stenosis in human subjects cannot be drawn. The included preclinical studies are however encouraging for further research.

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          Most cited references19

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          Mesenchymal Stromal Cells: Current Understanding and Clinical Status

          Multipotent mesenchymal stromal cells (MSCs) represent a rare heterogeneous subset of pluripotent stromal cells that can be isolated from many different adult tissues that exhibit the potential to give rise to cells of diverse lineages. Numerous studies have reported beneficial effects of MSCs in tissue repair and regeneration. After culture expansion and in vivo administration, MSCs home to and engraft to injured tissues and modulate the inflammatory response through synergistic downregulation of proinflammatory cytokines and upregulation of both prosurvival and antiinflammatory factors. In addition, MSCs possess remarkable immunosuppressive properties, suppressing T-cell, NK cell functions, and also modulating dentritic cell activities. Tremendous progress has been made in preclinical studies using MSCs, including the ability to use allogeneic cells, which has driven the application of MSCs toward the clinical setting. This review highlights our current understanding into the biology of MSCs with particular emphasis on the cardiovascular and renal applications, and provides a brief update on the clinical status of MSC-based therapy.
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            Where is the evidence that animal research benefits humans?

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              Why animal studies are often poor predictors of human reactions to exposure.

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 September 2017
                2017
                : 12
                : 9
                : e0185283
                Affiliations
                [1 ] Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
                [2 ] Cell Therapy Facility, Blood Bank, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
                Università degli Studi della Campania "Luigi Vanvitelli", ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-0336-5411
                Article
                PONE-D-17-18956
                10.1371/journal.pone.0185283
                5608394
                28934345
                c8786b3f-d689-4cdf-985e-b1b59260f8bb
                © 2017 Jakobsen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 May 2017
                : 8 September 2017
                Page count
                Figures: 0, Tables: 2, Pages: 10
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100008363, Kræftens Bekæmpelse;
                Award ID: R165-A10483-16-S7
                Award Recipient :
                This work was funded by The Danish Cancer Society (Grant number: R165-A10483-16-S7) and The University of Copenhagen (Grant number: A5090). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Stem Cells
                Mesenchymal Stem Cells
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Stenosis
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Stenosis
                Biology and Life Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Inflammation
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Inflammation
                Research and Analysis Methods
                Experimental Organism Systems
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Experimental Organism Systems
                Animal Models
                Mouse Models
                Biology and Life Sciences
                Anatomy
                Respiratory System
                Trachea
                Medicine and Health Sciences
                Anatomy
                Respiratory System
                Trachea
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Tissue Repair
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Tissue Repair
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Bone Marrow
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Bone Marrow
                Biology and Life Sciences
                Immunology
                Immune System
                Bone Marrow
                Medicine and Health Sciences
                Immunology
                Immune System
                Bone Marrow
                Medicine and Health Sciences
                Clinical Genetics
                Stem Cell Therapy
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                All relevant data are within the paper.

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