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      Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice

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          Abstract

          Background

          The avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans. Avian influenza is characterized by pronounced activation of the proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory response syndrome and pulmonary infection in animals and humans. There are currently no specific treatment strategies for avian influenza.

          Methods

          We hypothesized that mesenchymal stromal cells (MSCs) would have beneficial effects in the treatment of H9N2 AIV-induced acute lung injury in mice. Six- to 8-week-old C57BL/6 mice were infected intranasally with 1 × 10 4 MID 50 of A/HONG KONG/2108/2003 [H9N2 (HK)] H9N2 virus to induce acute lung injury. After 30 min, syngeneic MSCs were delivered through the caudal vein. Three days after infection, we measured the survival rate, lung weight, arterial blood gas, and cytokines in both bronchoalveolar lavage fluid (BALF) and serum, and assessed pathological changes to the lungs.

          Results

          MSC administration significantly palliated H9N2 AIV-induced pulmonary inflammation by reducing chemokines and proinflammatory cytokines levels, as well as reducing inflammatory cell recruit into the lungs. Thus, H9N2 AIV-induced lung injury was markedly alleviated in mice treated with MSCs. Lung histopathology and arterial blood gas analysis were improved in mice with H9N2 AIV-induced lung injury following MSC treatment.

          Conclusions

          MSC treatment significantly reduces H9N2 AIV-induced acute lung injury in mice and is associated with reduced pulmonary inflammation. These results indicate a potential role for MSC therapy in the treatment of clinical avian influenza.

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          Most cited references37

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          Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates.

          In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1 (chicken) virus resulted in the deaths of six individuals and once again raised the specter of a potentially devastating influenza pandemic. Slaughter of the poultry in the live bird markets removed the source of infection and no further human cases of H5N1 infection have occurred. In March 1999, however, a new pandemic threat appeared when influenza A H9N2 viruses infected two children in Hong Kong. These two virus isolates are similar to an H9N2 virus isolated from a quail in Hong Kong in late 1997. Although differing in their surface hemagglutinin and neuraminidase components, a notable feature of these H9N2 viruses is that the six genes encoding the internal components of the virus are similar to those of the 1997 H5N1 human and avian isolates. This common feature emphasizes the apparent propensity of avian viruses with this genetic complement to infect humans and highlights the potential for the emergence of a novel human pathogen.
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            Human infection with influenza H9N2.

            We report the clinical features of two cases of human infection with influenza A virus subtype H9N2 in Hong Kong, and show that serum samples from blood donors in Hong Kong had neutralising antibody suggestive of prior infection with influenza H9N2.
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              Wharton’s Jelly-Derived Mesenchymal Stem Cells: Phenotypic Characterization and Optimizing Their Therapeutic Potential for Clinical Applications

              Wharton’s jelly (WJ) is a gelatinous tissue within the umbilical cord that contains myofibroblast-like stromal cells. A unique cell population of WJ that has been suggested as displaying the stemness phenotype is the mesenchymal stromal cells (MSCs). Because MSCs’ stemness and immune properties appear to be more robustly expressed and functional which are more comparable with fetal than adult-derived MSCs, MSCs harvested from the “young” WJ are considered much more proliferative, immunosuppressive, and even therapeutically active stem cells than those isolated from older, adult tissue sources such as the bone marrow or adipose. The present review discusses the phenotypic characteristics, therapeutic applications, and optimization of experimental protocols for WJ-derived stem cells. MSCs derived from WJ display promising transplantable features, including ease of sourcing, in vitro expandability, differentiation abilities, immune-evasion and immune-regulation capacities. Accumulating evidence demonstrates that WJ-derived stem cells possess many potential advantages as transplantable cells for treatment of various diseases (e.g., cancer, chronic liver disease, cardiovascular diseases, nerve, cartilage and tendon injury). Additional studies are warranted to translate the use of WJ-derived stem cells for clinical applications.
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                Author and article information

                Contributors
                liyan.nju@163.com , liyan@jscdc.cn
                xujun@jscdc.cn
                shiwq@jscdc.cn
                chencheng@jscdc.cn
                shaoyan@jscdc.cn
                zhulimei@jscdc.cn
                luwei@jscdc.cn
                +86-25-83686497 , hanxd@nju.edu.cn
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                28 October 2016
                28 October 2016
                2016
                : 7
                : 159
                Affiliations
                [1 ]Department of Chronic Communicable Disease, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, 210009 People’s Republic of China
                [2 ]Medical School, Nanjing University, Nanjing, Jiangsu 210093 People’s Republic of China
                [3 ]Institute of Toxicology & Functional Assessment, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, 210009 People’s Republic of China
                Article
                395
                10.1186/s13287-016-0395-z
                5084318
                27793190
                4ecdbc82-b07d-438f-9614-f5db80a298e1
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 June 2016
                : 3 August 2016
                : 24 August 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81301448
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Molecular medicine
                mesenchymal stromal cell,h9n2 avian influenza viruses,lung injury,cell therapy

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