Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Sen Ren, Jing Chen, Dominik Duscher, Yutian Liu, Guojun Guo, Yu Kang, Hewei Xiong, Peng Zhan, Yang Wang, Cheng Wang, Hans-Günther Machens, Zhenbing Chen

ABSTRACT

BACKGROUND: Human adipose stem cells (ASCs) have emerged as a promising treatment paradigm for skin wounds. Recent works demonstrate that the therapeutic effect of stem cells is partially mediated by extracellular vesicles, which comprise exosomes and microvesicles. In this study, we investigate the regenerative effects of isolated microvesicles from ASCs and evaluate the mechanisms how ASC microvesicles promote wound healing. METHODS: Adipose stem cell-derived microvesicles (ASC-MVs) were isolated by differential ultracentrifugation, stained by PKH26, and characterized by electron microscopy and dynamic light scattering (DLS). We examined ASC-MV effects on proliferation, migration, and angiogenesis of keratinocytes, fibroblasts, and endothelial cells both in vitro and in vivo. Next, we explored the underlying mechanisms by gene expression analysis and the activation levels of AKT and ERK signaling pathways in all three kinds of cells after ASC-MV stimulation. We then assessed the effect of ASC-MVs on collagen deposition, neovascularization, and re-epithelialization in an in vivo skin injury model. RESULTS: ASC-MVs could be readily internalized by human umbilical vein endothelial cells (HUVECs), HaCAT, and fibroblasts and significantly promoted the proliferation, migration, and angiogenesis of these cells both in vitro and in vivo. The gene expression of proliferative markers (cyclin D1, cyclin D2, cyclin A1, cyclin A2) and growth factors (VEGFA, PDGFA, EGF, FGF2) was significantly upregulated after ASC-MV treatment. Importantly, ASC-MVs stimulated the activation of AKT and ERK signaling pathways in those cells. The local injection of ASC-MVs at wound sites significantly increased the re-epithelialization, collagen deposition, and neovascularization and led to accelerated wound closure. CONCLUSIONS: Our data suggest that ASC-MVs can stimulate HUVEC, HaCAT, and fibroblast functions. ASC-MV therapy significantly accelerates wound healing, and the benefits of ASC-MVs may due to the involvement of AKT and ERK signaling pathways. This illustrates the therapeutic potential of ASC-MVs which may become a novel treatment paradigm for cutaneous wound healing. More... »

PAGES

47

References to SciGraph publications

  • 2017-08. Pro-angiogenic capacities of microvesicles produced by skin wound myofibroblasts in ANGIOGENESIS
  • 2016-12. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts in SCIENTIFIC REPORTS
  • 2009-01. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources in NATURE PROTOCOLS
  • 2016-06-15. Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation in NATURE COMMUNICATIONS
  • 2014-03. Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis in STEM CELL RESEARCH & THERAPY
  • 2013-06. Cutaneous wound healing: recruiting developmental pathways for regeneration in CELLULAR AND MOLECULAR LIFE SCIENCES
  • 2017-12. Notch1 Signaling Contributes to Hypoxia-induced High Expression of Integrin β1 in Keratinocyte Migration in SCIENTIFIC REPORTS
  • 2016-12. Localization of human adipose-derived stem cells and their effect in repair of diabetic foot ulcers in rats in STEM CELL RESEARCH & THERAPY
  • 2018-12. Exosomes from acellular Wharton’s jelly of the human umbilical cord promotes skin wound healing in STEM CELL RESEARCH & THERAPY
  • 2013-05. Extracellular vesicles: biology and emerging therapeutic opportunities in NATURE REVIEWS DRUG DISCOVERY
  • 2015-05. Aging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells in SCIENTIFIC REPORTS
  • 2006-02. Common markers of proliferation in NATURE REVIEWS CANCER
  • 2017-12. Therapeutic angiogenesis of adipose-derived stem cells for ischemic diseases in STEM CELL RESEARCH & THERAPY
  • 2018-01-17. Shedding light on the cell biology of extracellular vesicles in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2015-12. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis in JOURNAL OF TRANSLATIONAL MEDICINE
  • 2008-05-15. Wound repair and regeneration in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13287-019-1152-x

    DOI

    http://dx.doi.org/10.1186/s13287-019-1152-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111831636

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30704535


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ren", 
            "givenName": "Sen", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chen", 
            "givenName": "Jing", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Technical University Munich", 
              "id": "https://www.grid.ac/institutes/grid.6936.a", 
              "name": [
                "Department of Plastic and Hand Surgery, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Duscher", 
            "givenName": "Dominik", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Liu", 
            "givenName": "Yutian", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Guo", 
            "givenName": "Guojun", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kang", 
            "givenName": "Yu", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Xiong", 
            "givenName": "Hewei", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zhan", 
            "givenName": "Peng", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wang", 
            "givenName": "Yang", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wang", 
            "givenName": "Cheng", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Technical University Munich", 
              "id": "https://www.grid.ac/institutes/grid.6936.a", 
              "name": [
                "Department of Plastic and Hand Surgery, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Machens", 
            "givenName": "Hans-G\u00fcnther", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Huazhong University of Science and Technology", 
              "id": "https://www.grid.ac/institutes/grid.33199.31", 
              "name": [
                "Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chen", 
            "givenName": "Zhenbing", 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/srep07144", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000597127", 
              "https://doi.org/10.1038/srep07144"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.bbagrm.2014.03.013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002432260"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/stem.1771", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006569024"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/scrt391", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015975855", 
              "https://doi.org/10.1186/scrt391"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep32993", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020248882", 
              "https://doi.org/10.1038/srep32993"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/stem.1076", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024629404"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.jdiacomp.2016.05.009", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025923287"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12967-015-0417-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026406777", 
              "https://doi.org/10.1186/s12967-015-0417-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12967-015-0417-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026406777", 
              "https://doi.org/10.1186/s12967-015-0417-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd3978", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027869587", 
              "https://doi.org/10.1038/nrd3978"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/prs.0000000000002773", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028447832"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/prs.0000000000002773", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028447832"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature07039", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030873761", 
              "https://doi.org/10.1038/nature07039"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejm199909023411006", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031369335"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1159/000381877", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032329852"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13287-016-0412-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034474584", 
              "https://doi.org/10.1186/s13287-016-0412-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13287-016-0412-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034474584", 
              "https://doi.org/10.1186/s13287-016-0412-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.15283/ijsc.2015.8.1.54", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039304268"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2008.211", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039987283", 
              "https://doi.org/10.1038/nprot.2008.211"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0140-6736(05)67700-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043600871"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms11958", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044346449", 
              "https://doi.org/10.1038/ncomms11958"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.bbrc.2015.09.166", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045057814"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc1802", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046303336", 
              "https://doi.org/10.1038/nrc1802"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc1802", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046303336", 
              "https://doi.org/10.1038/nrc1802"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00018-012-1152-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046955249", 
              "https://doi.org/10.1007/s00018-012-1152-9"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/gkn923", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047610281"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.drudis.2015.01.005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048555028"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.mcn.2008.03.009", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051285991"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stem.2015.06.007", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051441886"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-15-2120", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1063215939"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci81135", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1063419589"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.7150/ijbs.15514", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1073618578"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep43926", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084131829", 
              "https://doi.org/10.1038/srep43926"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10456-017-9554-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084518307", 
              "https://doi.org/10.1007/s10456-017-9554-9"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10456-017-9554-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084518307", 
              "https://doi.org/10.1007/s10456-017-9554-9"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1159/000475651", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085119093"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13287-017-0578-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085862927", 
              "https://doi.org/10.1186/s13287-017-0578-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13287-017-0578-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085862927", 
              "https://doi.org/10.1186/s13287-017-0578-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.jconrel.2017.08.022", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091286592"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1161/circresaha.117.311769", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092595735"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1161/circresaha.117.311769", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092595735"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/jcp.26426", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100289089"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrm.2017.125", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100456899", 
              "https://doi.org/10.1038/nrm.2017.125"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acs.chemrev.7b00534", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100712197"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acs.chemrev.7b00534", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100712197"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acs.chemrev.7b00534", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100712197"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.addr.2018.01.018", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100769952"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.yexcr.2018.06.035", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105202532"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13287-018-0921-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105552717", 
              "https://doi.org/10.1186/s13287-018-0921-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13287-018-0921-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105552717", 
              "https://doi.org/10.1186/s13287-018-0921-2"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-12", 
        "datePublishedReg": "2019-12-01", 
        "description": "BACKGROUND: Human adipose stem cells (ASCs) have emerged as a promising treatment paradigm for skin wounds. Recent works demonstrate that the therapeutic effect of stem cells is partially mediated by extracellular vesicles, which comprise exosomes and microvesicles. In this study, we investigate the regenerative effects of isolated microvesicles from ASCs and evaluate the mechanisms how ASC microvesicles promote wound healing.\nMETHODS: Adipose stem cell-derived microvesicles (ASC-MVs) were isolated by differential ultracentrifugation, stained by PKH26, and characterized by electron microscopy and dynamic light scattering (DLS). We examined ASC-MV effects on proliferation, migration, and angiogenesis of keratinocytes, fibroblasts, and endothelial cells both in vitro and in vivo. Next, we explored the underlying mechanisms by gene expression analysis and the activation levels of AKT and ERK signaling pathways in all three kinds of cells after ASC-MV stimulation. We then assessed the effect of ASC-MVs on collagen deposition, neovascularization, and re-epithelialization in an in vivo skin injury model.\nRESULTS: ASC-MVs could be readily internalized by human umbilical vein endothelial cells (HUVECs), HaCAT, and fibroblasts and significantly promoted the proliferation, migration, and angiogenesis of these cells both in vitro and in vivo. The gene expression of proliferative markers (cyclin D1, cyclin D2, cyclin A1, cyclin A2) and growth factors (VEGFA, PDGFA, EGF, FGF2) was significantly upregulated after ASC-MV treatment. Importantly, ASC-MVs stimulated the activation of AKT and ERK signaling pathways in those cells. The local injection of ASC-MVs at wound sites significantly increased the re-epithelialization, collagen deposition, and neovascularization and led to accelerated wound closure.\nCONCLUSIONS: Our data suggest that ASC-MVs can stimulate HUVEC, HaCAT, and fibroblast functions. ASC-MV therapy significantly accelerates wound healing, and the benefits of ASC-MVs may due to the involvement of AKT and ERK signaling pathways. This illustrates the therapeutic potential of ASC-MVs which may become a novel treatment paradigm for cutaneous wound healing.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1186/s13287-019-1152-x", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.7196646", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.4955066", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1043222", 
            "issn": [
              "1757-6512"
            ], 
            "name": "Stem Cell Research & Therapy", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "10"
          }
        ], 
        "name": "Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways", 
        "pagination": "47", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "e86bdbb69b114d0b13af766bc35f6f755436853bf9e5cc1e7c57fa09ae9f4d65"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "30704535"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101527581"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1186/s13287-019-1152-x"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1111831636"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1186/s13287-019-1152-x", 
          "https://app.dimensions.ai/details/publication/pub.1111831636"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T09:02", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000331_0000000331/records_105427_00000000.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://link.springer.com/10.1186%2Fs13287-019-1152-x"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s13287-019-1152-x'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s13287-019-1152-x'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s13287-019-1152-x'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s13287-019-1152-x'


     

    This table displays all metadata directly associated to this object as RDF triples.

    276 TRIPLES      21 PREDICATES      69 URIs      21 LITERALS      9 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1186/s13287-019-1152-x schema:about anzsrc-for:06
    2 anzsrc-for:0601
    3 schema:author Nf7b6d161de744acfbad16d4465082d6d
    4 schema:citation sg:pub.10.1007/s00018-012-1152-9
    5 sg:pub.10.1007/s10456-017-9554-9
    6 sg:pub.10.1038/nature07039
    7 sg:pub.10.1038/ncomms11958
    8 sg:pub.10.1038/nprot.2008.211
    9 sg:pub.10.1038/nrc1802
    10 sg:pub.10.1038/nrd3978
    11 sg:pub.10.1038/nrm.2017.125
    12 sg:pub.10.1038/srep07144
    13 sg:pub.10.1038/srep32993
    14 sg:pub.10.1038/srep43926
    15 sg:pub.10.1186/s12967-015-0417-0
    16 sg:pub.10.1186/s13287-016-0412-2
    17 sg:pub.10.1186/s13287-017-0578-2
    18 sg:pub.10.1186/s13287-018-0921-2
    19 sg:pub.10.1186/scrt391
    20 https://doi.org/10.1002/jcp.26426
    21 https://doi.org/10.1002/stem.1076
    22 https://doi.org/10.1002/stem.1771
    23 https://doi.org/10.1016/j.addr.2018.01.018
    24 https://doi.org/10.1016/j.bbagrm.2014.03.013
    25 https://doi.org/10.1016/j.bbrc.2015.09.166
    26 https://doi.org/10.1016/j.drudis.2015.01.005
    27 https://doi.org/10.1016/j.jconrel.2017.08.022
    28 https://doi.org/10.1016/j.jdiacomp.2016.05.009
    29 https://doi.org/10.1016/j.mcn.2008.03.009
    30 https://doi.org/10.1016/j.stem.2015.06.007
    31 https://doi.org/10.1016/j.yexcr.2018.06.035
    32 https://doi.org/10.1016/s0140-6736(05)67700-8
    33 https://doi.org/10.1021/acs.chemrev.7b00534
    34 https://doi.org/10.1056/nejm199909023411006
    35 https://doi.org/10.1093/nar/gkn923
    36 https://doi.org/10.1097/prs.0000000000002773
    37 https://doi.org/10.1158/0008-5472.can-15-2120
    38 https://doi.org/10.1159/000381877
    39 https://doi.org/10.1159/000475651
    40 https://doi.org/10.1161/circresaha.117.311769
    41 https://doi.org/10.1172/jci81135
    42 https://doi.org/10.15283/ijsc.2015.8.1.54
    43 https://doi.org/10.7150/ijbs.15514
    44 schema:datePublished 2019-12
    45 schema:datePublishedReg 2019-12-01
    46 schema:description BACKGROUND: Human adipose stem cells (ASCs) have emerged as a promising treatment paradigm for skin wounds. Recent works demonstrate that the therapeutic effect of stem cells is partially mediated by extracellular vesicles, which comprise exosomes and microvesicles. In this study, we investigate the regenerative effects of isolated microvesicles from ASCs and evaluate the mechanisms how ASC microvesicles promote wound healing. METHODS: Adipose stem cell-derived microvesicles (ASC-MVs) were isolated by differential ultracentrifugation, stained by PKH26, and characterized by electron microscopy and dynamic light scattering (DLS). We examined ASC-MV effects on proliferation, migration, and angiogenesis of keratinocytes, fibroblasts, and endothelial cells both in vitro and in vivo. Next, we explored the underlying mechanisms by gene expression analysis and the activation levels of AKT and ERK signaling pathways in all three kinds of cells after ASC-MV stimulation. We then assessed the effect of ASC-MVs on collagen deposition, neovascularization, and re-epithelialization in an in vivo skin injury model. RESULTS: ASC-MVs could be readily internalized by human umbilical vein endothelial cells (HUVECs), HaCAT, and fibroblasts and significantly promoted the proliferation, migration, and angiogenesis of these cells both in vitro and in vivo. The gene expression of proliferative markers (cyclin D1, cyclin D2, cyclin A1, cyclin A2) and growth factors (VEGFA, PDGFA, EGF, FGF2) was significantly upregulated after ASC-MV treatment. Importantly, ASC-MVs stimulated the activation of AKT and ERK signaling pathways in those cells. The local injection of ASC-MVs at wound sites significantly increased the re-epithelialization, collagen deposition, and neovascularization and led to accelerated wound closure. CONCLUSIONS: Our data suggest that ASC-MVs can stimulate HUVEC, HaCAT, and fibroblast functions. ASC-MV therapy significantly accelerates wound healing, and the benefits of ASC-MVs may due to the involvement of AKT and ERK signaling pathways. This illustrates the therapeutic potential of ASC-MVs which may become a novel treatment paradigm for cutaneous wound healing.
    47 schema:genre research_article
    48 schema:inLanguage en
    49 schema:isAccessibleForFree true
    50 schema:isPartOf N537ae641e8d2470abb0304daa6aab81f
    51 Na43230e046024f41b0cbfb44c40c28dc
    52 sg:journal.1043222
    53 schema:name Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways
    54 schema:pagination 47
    55 schema:productId N0bf4b664bc3142abadb0379f0527585e
    56 N1ddad83be1af4d12bcdb70311ba2d898
    57 N3b0a395560a144889409a2544fb76778
    58 N613303db265245eaab67d5a4a13e6e97
    59 Nbdf9d2c5b33b4b52bb8991ba9206ed39
    60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111831636
    61 https://doi.org/10.1186/s13287-019-1152-x
    62 schema:sdDatePublished 2019-04-11T09:02
    63 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    64 schema:sdPublisher Nff23f8c35ff24064ac702a2e698eb931
    65 schema:url https://link.springer.com/10.1186%2Fs13287-019-1152-x
    66 sgo:license sg:explorer/license/
    67 sgo:sdDataset articles
    68 rdf:type schema:ScholarlyArticle
    69 N012532e72e444fd98cec93a8b4ac2838 rdf:first N31a9cb2cbc8d41048523ecbd689b8e62
    70 rdf:rest N61a15f806cde48a98437f257f002a7be
    71 N0bf4b664bc3142abadb0379f0527585e schema:name doi
    72 schema:value 10.1186/s13287-019-1152-x
    73 rdf:type schema:PropertyValue
    74 N0e901863f6a74a219a7abfa06351b2f7 rdf:first N5528f213663d4ce2ae685a3c6e2771c5
    75 rdf:rest N8582a59172f64cf6aacc23d6c622732d
    76 N1560627d62034e298dce7e8f8fc4b4ad rdf:first N7230ad10a409456da5804c704bcd9b51
    77 rdf:rest Nb0ca1c1281894124a3755f847ed0b85e
    78 N1ddad83be1af4d12bcdb70311ba2d898 schema:name nlm_unique_id
    79 schema:value 101527581
    80 rdf:type schema:PropertyValue
    81 N2721166729d547618a1686edc0c567ab schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    82 schema:familyName Xiong
    83 schema:givenName Hewei
    84 rdf:type schema:Person
    85 N31a9cb2cbc8d41048523ecbd689b8e62 schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    86 schema:familyName Kang
    87 schema:givenName Yu
    88 rdf:type schema:Person
    89 N3b0a395560a144889409a2544fb76778 schema:name pubmed_id
    90 schema:value 30704535
    91 rdf:type schema:PropertyValue
    92 N410f3c3f50654250a6f84914163dca08 schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    93 schema:familyName Wang
    94 schema:givenName Cheng
    95 rdf:type schema:Person
    96 N537ae641e8d2470abb0304daa6aab81f schema:issueNumber 1
    97 rdf:type schema:PublicationIssue
    98 N5528f213663d4ce2ae685a3c6e2771c5 schema:affiliation https://www.grid.ac/institutes/grid.6936.a
    99 schema:familyName Machens
    100 schema:givenName Hans-Günther
    101 rdf:type schema:Person
    102 N613303db265245eaab67d5a4a13e6e97 schema:name dimensions_id
    103 schema:value pub.1111831636
    104 rdf:type schema:PropertyValue
    105 N61a15f806cde48a98437f257f002a7be rdf:first N2721166729d547618a1686edc0c567ab
    106 rdf:rest N77fc373480744578a41132f70b8eccca
    107 N6c984d899b11413ab92480ba69f158cc schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    108 schema:familyName Chen
    109 schema:givenName Jing
    110 rdf:type schema:Person
    111 N6dc518965ecb4d41a105efa8eefebf77 rdf:first N410f3c3f50654250a6f84914163dca08
    112 rdf:rest N0e901863f6a74a219a7abfa06351b2f7
    113 N7230ad10a409456da5804c704bcd9b51 schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    114 schema:familyName Liu
    115 schema:givenName Yutian
    116 rdf:type schema:Person
    117 N73e4e7bfbc13400280dae981299417c7 rdf:first N6c984d899b11413ab92480ba69f158cc
    118 rdf:rest Ne0b985eaa1ff48cb9546b783dba29e89
    119 N77fc373480744578a41132f70b8eccca rdf:first Nbfd8a19f8d224bc681fb094f5a0e2c2f
    120 rdf:rest N79d81ffd22c04adfa79e92561a6709de
    121 N79d81ffd22c04adfa79e92561a6709de rdf:first N9ce73d700a1f4ae88d8b82b67e3a2822
    122 rdf:rest N6dc518965ecb4d41a105efa8eefebf77
    123 N7e6c5d54e47c4cfabe4048118be5da1f schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    124 schema:familyName Ren
    125 schema:givenName Sen
    126 rdf:type schema:Person
    127 N8582a59172f64cf6aacc23d6c622732d rdf:first N88ec58c11f2c4a79be5eaecac0831312
    128 rdf:rest rdf:nil
    129 N88ec58c11f2c4a79be5eaecac0831312 schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    130 schema:familyName Chen
    131 schema:givenName Zhenbing
    132 rdf:type schema:Person
    133 N9ce73d700a1f4ae88d8b82b67e3a2822 schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    134 schema:familyName Wang
    135 schema:givenName Yang
    136 rdf:type schema:Person
    137 Na20f6dd6c10a4181aee4bd79db71cad3 schema:affiliation https://www.grid.ac/institutes/grid.6936.a
    138 schema:familyName Duscher
    139 schema:givenName Dominik
    140 rdf:type schema:Person
    141 Na43230e046024f41b0cbfb44c40c28dc schema:volumeNumber 10
    142 rdf:type schema:PublicationVolume
    143 Nb0ca1c1281894124a3755f847ed0b85e rdf:first Nc125525031fa4af48fa331d72055d980
    144 rdf:rest N012532e72e444fd98cec93a8b4ac2838
    145 Nbdf9d2c5b33b4b52bb8991ba9206ed39 schema:name readcube_id
    146 schema:value e86bdbb69b114d0b13af766bc35f6f755436853bf9e5cc1e7c57fa09ae9f4d65
    147 rdf:type schema:PropertyValue
    148 Nbfd8a19f8d224bc681fb094f5a0e2c2f schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    149 schema:familyName Zhan
    150 schema:givenName Peng
    151 rdf:type schema:Person
    152 Nc125525031fa4af48fa331d72055d980 schema:affiliation https://www.grid.ac/institutes/grid.33199.31
    153 schema:familyName Guo
    154 schema:givenName Guojun
    155 rdf:type schema:Person
    156 Ne0b985eaa1ff48cb9546b783dba29e89 rdf:first Na20f6dd6c10a4181aee4bd79db71cad3
    157 rdf:rest N1560627d62034e298dce7e8f8fc4b4ad
    158 Nf7b6d161de744acfbad16d4465082d6d rdf:first N7e6c5d54e47c4cfabe4048118be5da1f
    159 rdf:rest N73e4e7bfbc13400280dae981299417c7
    160 Nff23f8c35ff24064ac702a2e698eb931 schema:name Springer Nature - SN SciGraph project
    161 rdf:type schema:Organization
    162 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    163 schema:name Biological Sciences
    164 rdf:type schema:DefinedTerm
    165 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    166 schema:name Biochemistry and Cell Biology
    167 rdf:type schema:DefinedTerm
    168 sg:grant.4955066 http://pending.schema.org/fundedItem sg:pub.10.1186/s13287-019-1152-x
    169 rdf:type schema:MonetaryGrant
    170 sg:grant.7196646 http://pending.schema.org/fundedItem sg:pub.10.1186/s13287-019-1152-x
    171 rdf:type schema:MonetaryGrant
    172 sg:journal.1043222 schema:issn 1757-6512
    173 schema:name Stem Cell Research & Therapy
    174 rdf:type schema:Periodical
    175 sg:pub.10.1007/s00018-012-1152-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046955249
    176 https://doi.org/10.1007/s00018-012-1152-9
    177 rdf:type schema:CreativeWork
    178 sg:pub.10.1007/s10456-017-9554-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084518307
    179 https://doi.org/10.1007/s10456-017-9554-9
    180 rdf:type schema:CreativeWork
    181 sg:pub.10.1038/nature07039 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030873761
    182 https://doi.org/10.1038/nature07039
    183 rdf:type schema:CreativeWork
    184 sg:pub.10.1038/ncomms11958 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044346449
    185 https://doi.org/10.1038/ncomms11958
    186 rdf:type schema:CreativeWork
    187 sg:pub.10.1038/nprot.2008.211 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039987283
    188 https://doi.org/10.1038/nprot.2008.211
    189 rdf:type schema:CreativeWork
    190 sg:pub.10.1038/nrc1802 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046303336
    191 https://doi.org/10.1038/nrc1802
    192 rdf:type schema:CreativeWork
    193 sg:pub.10.1038/nrd3978 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027869587
    194 https://doi.org/10.1038/nrd3978
    195 rdf:type schema:CreativeWork
    196 sg:pub.10.1038/nrm.2017.125 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100456899
    197 https://doi.org/10.1038/nrm.2017.125
    198 rdf:type schema:CreativeWork
    199 sg:pub.10.1038/srep07144 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000597127
    200 https://doi.org/10.1038/srep07144
    201 rdf:type schema:CreativeWork
    202 sg:pub.10.1038/srep32993 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020248882
    203 https://doi.org/10.1038/srep32993
    204 rdf:type schema:CreativeWork
    205 sg:pub.10.1038/srep43926 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084131829
    206 https://doi.org/10.1038/srep43926
    207 rdf:type schema:CreativeWork
    208 sg:pub.10.1186/s12967-015-0417-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026406777
    209 https://doi.org/10.1186/s12967-015-0417-0
    210 rdf:type schema:CreativeWork
    211 sg:pub.10.1186/s13287-016-0412-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034474584
    212 https://doi.org/10.1186/s13287-016-0412-2
    213 rdf:type schema:CreativeWork
    214 sg:pub.10.1186/s13287-017-0578-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085862927
    215 https://doi.org/10.1186/s13287-017-0578-2
    216 rdf:type schema:CreativeWork
    217 sg:pub.10.1186/s13287-018-0921-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105552717
    218 https://doi.org/10.1186/s13287-018-0921-2
    219 rdf:type schema:CreativeWork
    220 sg:pub.10.1186/scrt391 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015975855
    221 https://doi.org/10.1186/scrt391
    222 rdf:type schema:CreativeWork
    223 https://doi.org/10.1002/jcp.26426 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100289089
    224 rdf:type schema:CreativeWork
    225 https://doi.org/10.1002/stem.1076 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024629404
    226 rdf:type schema:CreativeWork
    227 https://doi.org/10.1002/stem.1771 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006569024
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.1016/j.addr.2018.01.018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100769952
    230 rdf:type schema:CreativeWork
    231 https://doi.org/10.1016/j.bbagrm.2014.03.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002432260
    232 rdf:type schema:CreativeWork
    233 https://doi.org/10.1016/j.bbrc.2015.09.166 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045057814
    234 rdf:type schema:CreativeWork
    235 https://doi.org/10.1016/j.drudis.2015.01.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048555028
    236 rdf:type schema:CreativeWork
    237 https://doi.org/10.1016/j.jconrel.2017.08.022 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091286592
    238 rdf:type schema:CreativeWork
    239 https://doi.org/10.1016/j.jdiacomp.2016.05.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025923287
    240 rdf:type schema:CreativeWork
    241 https://doi.org/10.1016/j.mcn.2008.03.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051285991
    242 rdf:type schema:CreativeWork
    243 https://doi.org/10.1016/j.stem.2015.06.007 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051441886
    244 rdf:type schema:CreativeWork
    245 https://doi.org/10.1016/j.yexcr.2018.06.035 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105202532
    246 rdf:type schema:CreativeWork
    247 https://doi.org/10.1016/s0140-6736(05)67700-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043600871
    248 rdf:type schema:CreativeWork
    249 https://doi.org/10.1021/acs.chemrev.7b00534 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100712197
    250 rdf:type schema:CreativeWork
    251 https://doi.org/10.1056/nejm199909023411006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031369335
    252 rdf:type schema:CreativeWork
    253 https://doi.org/10.1093/nar/gkn923 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047610281
    254 rdf:type schema:CreativeWork
    255 https://doi.org/10.1097/prs.0000000000002773 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028447832
    256 rdf:type schema:CreativeWork
    257 https://doi.org/10.1158/0008-5472.can-15-2120 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063215939
    258 rdf:type schema:CreativeWork
    259 https://doi.org/10.1159/000381877 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032329852
    260 rdf:type schema:CreativeWork
    261 https://doi.org/10.1159/000475651 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085119093
    262 rdf:type schema:CreativeWork
    263 https://doi.org/10.1161/circresaha.117.311769 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092595735
    264 rdf:type schema:CreativeWork
    265 https://doi.org/10.1172/jci81135 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063419589
    266 rdf:type schema:CreativeWork
    267 https://doi.org/10.15283/ijsc.2015.8.1.54 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039304268
    268 rdf:type schema:CreativeWork
    269 https://doi.org/10.7150/ijbs.15514 schema:sameAs https://app.dimensions.ai/details/publication/pub.1073618578
    270 rdf:type schema:CreativeWork
    271 https://www.grid.ac/institutes/grid.33199.31 schema:alternateName Huazhong University of Science and Technology
    272 schema:name Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China
    273 rdf:type schema:Organization
    274 https://www.grid.ac/institutes/grid.6936.a schema:alternateName Technical University Munich
    275 schema:name Department of Plastic and Hand Surgery, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany
    276 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...