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Related Experiment Video

Updated: Dec 18, 2025

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Therapeutic Reversal of Radiotherapy Injury to Pro-fibrotic Dysfunctional Fibroblasts In Vitro Using Adipose-derived

Lipi Shukla1,2,3,4, Rodney Luwor5, Matthew E Ritchie6

  • 1Regenerative Surgery and Lymphatics Department, O'Brien Institute, St. Vincent's Institute, Fitzroy, Victoria, Australia.

Plastic and Reconstructive Surgery. Global Open
|June 16, 2020
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Summary

Radiotherapy (RTx) causes fibrosis by altering fibroblast function. Adipose-derived stem cell secretomes can reverse these radiation-induced changes, offering potential treatments for fibrotic diseases.

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Area of Science:

  • Fibrosis research
  • Stem cell biology
  • Radiation oncology

Background:

  • Radiotherapy (RTx) is crucial for cancer survival but causes fibrotic injury to healthy tissues.
  • The mechanisms behind fat grafting's beneficial effects on RTx-induced fibrosis are not fully understood.
  • This study investigates how RTx affects fibroblast function and if adipose-derived stem cells (ADSC) can mitigate these effects.

Purpose of the Study:

  • To investigate cellular and molecular changes in fibroblasts after RTx.
  • To determine if ADSC secretomes can reverse RTx-induced fibroblast alterations.
  • To explore potential therapeutic strategies for RTx-induced fibrosis.

Main Methods:

  • Irradiation of normal human dermal fibroblasts (NHDF) with 10Gy.
  • Functional assays to assess fibroblast migration, adhesion, and contractility.
  • RNA-sequencing and targeted microarrays to analyze gene expression.
  • Treatment of irradiated fibroblasts with ADSC-conditioned media.

Main Results:

  • RTx induced significant changes in NHDF morphology and function, promoting a more invasive phenotype.
  • Gene expression analysis revealed alterations in collagen, MMP homeostasis, and cell-cycle progression.
  • ADSC-conditioned media effectively reversed the RTx-induced hypermigratory state of NHDF.
  • TGFβ was not identified as a key regulator of the fibroblast response.

Conclusions:

  • Irradiated fibroblast behavior explains clinical manifestations of RTx-induced fibrosis.
  • ADSC secretomes show potential for combating fibrosis in RTx patients.
  • These findings suggest ADSC secretomes could treat other fibrotic conditions.