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Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization.
Chinnapaka, Somaiah; Yang, Katherine S; Surucu, Yusuf; Bengur, Fuat B; Arellano, José A; Tirmizi, Zayaan; Malekzadeh, Hamid; Epperly, Michael W; Hou, Wen; Greenberger, Joel S; Rubin, J Peter; Ejaz, Asim.
Afiliación
  • Chinnapaka S; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Yang KS; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Surucu Y; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Bengur FB; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Arellano JA; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Tirmizi Z; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Malekzadeh H; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Epperly MW; Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
  • Hou W; Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
  • Greenberger JS; Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
  • Rubin JP; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Ejaz A; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
iScience ; 26(9): 107660, 2023 Sep 15.
Article en En | MEDLINE | ID: mdl-37705953
Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated adipose-derived extracellular matrix (Ad-ECM) as a mitigator of RISF. Female C57BL/6J mice that were irradiated developed fibrosis, which was mitigated by a single local Ad-ECM injection, improving limb movement and reducing epithelium thickness and collagen deposition. Ad-ECM treatment resulted in decreased expression of pro-inflammatory and fibrotic genes, and upregulation of anti-inflammatory cytokines, promoting M2 macrophage polarization. Co-culture of irradiated human fibroblasts with Ad-ECM down-modulated fibrotic gene expression and enhanced bone marrow cell migration. Ad-ECM treatment also increased interleukin (IL)-4, IL-5, and IL-15 expression in endothelial cells, stimulating M2 macrophage polarization and alleviating RISF. Prophylactic use of Ad-ECM showed effectiveness in mitigation. This study suggests Ad-ECM's potential in treating chronic-stage fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos