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

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2021
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Jäger, Niklas
Meier, Nicole
Meyer, Thimo
Neu, Adrian
Steinritz, Dirk
Thiermann, Horst
Schmidt, Annette
et al.
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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
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Senescence, Mesenchymal stem cells, Wound healing disorder, Chemical warfare agents, Sulfur mustard
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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}
}
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