Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard

Lade...
Vorschaubild
Dateien
Rothmiller_2-2sfvlufyv5oz5.pdf
Rothmiller_2-2sfvlufyv5oz5.pdfGröße: 6.6 MBDownloads: 199
Datum
2021
Autor:innen
Jäger, Niklas
Meier, Nicole
Meyer, Thimo
Neu, Adrian
Steinritz, Dirk
Thiermann, Horst
Schmidt, Annette
et al.
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Hybrid
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Archives of Toxicology. Springer. 2021, 95(2), pp. 727-747. ISSN 0340-5761. eISSN 1432-0738. Available under: doi: 10.1007/s00204-020-02946-5
Zusammenfassung

Wound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Senescence, Mesenchymal stem cells, Wound healing disorder, Chemical warfare agents, Sulfur mustard
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690ROTHMILLER, Simone, Niklas JÄGER, Nicole MEIER, Thimo MEYER, Adrian NEU, Dirk STEINRITZ, Horst THIERMANN, Aswin MANGERICH, Alexander BÜRKLE, Annette SCHMIDT, 2021. Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. In: Archives of Toxicology. Springer. 2021, 95(2), pp. 727-747. ISSN 0340-5761. eISSN 1432-0738. Available under: doi: 10.1007/s00204-020-02946-5
BibTex
@article{Rothmiller2021-02Chron-52592,
  year={2021},
  doi={10.1007/s00204-020-02946-5},
  title={Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard},
  number={2},
  volume={95},
  issn={0340-5761},
  journal={Archives of Toxicology},
  pages={727--747},
  author={Rothmiller, Simone and Jäger, Niklas and Meier, Nicole and Meyer, Thimo and Neu, Adrian and Steinritz, Dirk and Thiermann, Horst and Mangerich, Aswin and Bürkle, Alexander and Schmidt, Annette}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52592">
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/52592/1/Rothmiller_2-2sfvlufyv5oz5.pdf"/>
    <dc:contributor>Steinritz, Dirk</dc:contributor>
    <dc:creator>Meyer, Thimo</dc:creator>
    <dc:contributor>Thiermann, Horst</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Meyer, Thimo</dc:contributor>
    <dc:contributor>Meier, Nicole</dc:contributor>
    <dcterms:abstract xml:lang="eng">Wound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases.</dcterms:abstract>
    <dc:creator>Mangerich, Aswin</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Steinritz, Dirk</dc:creator>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dc:contributor>Bürkle, Alexander</dc:contributor>
    <dc:creator>Meier, Nicole</dc:creator>
    <dc:contributor>Neu, Adrian</dc:contributor>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/52592"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:title>Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard</dcterms:title>
    <dc:contributor>Jäger, Niklas</dc:contributor>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/52592/1/Rothmiller_2-2sfvlufyv5oz5.pdf"/>
    <dc:creator>Neu, Adrian</dc:creator>
    <dc:creator>Schmidt, Annette</dc:creator>
    <dc:contributor>Mangerich, Aswin</dc:contributor>
    <dc:contributor>Rothmiller, Simone</dc:contributor>
    <dc:language>eng</dc:language>
    <dc:creator>Rothmiller, Simone</dc:creator>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:contributor>Schmidt, Annette</dc:contributor>
    <dc:creator>Jäger, Niklas</dc:creator>
    <dcterms:issued>2021-02</dcterms:issued>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Bürkle, Alexander</dc:creator>
    <dc:creator>Thiermann, Horst</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-01-28T10:07:44Z</dcterms:available>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-01-28T10:07:44Z</dc:date>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen