Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium

Wanchao Chen; Yang Wang; Jiancheng Zheng; Yan Chen; Can Zhang; Wei Yang; Lingling Wu; Zeyu Yang; Yu Wang; Chunmeng Shi

doi:10.1093/burnst/tkad001

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Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium

更新时间：2023-08-29

- Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium
- Burns & Trauma Vol. 11, Issue 1, (2023)
- 作者机构：
  
  1. Institute of Rocket Force Medicine
  2. Third Military Medical University (Army Medical University)
  3. Breast and Thyroid Surgical Department, Chongqing General Hospital
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad001
  CLC：
- Published：2023，
  
  Published Online：11 May 2023，
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Wanchao Chen, Yang Wang, Jiancheng Zheng, Yan Chen, Can Zhang, Wei Yang, Lingling Wu, Zeyu Yang, Yu Wang, Chunmeng Shi, Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium, Burns & Trauma, Volume 11, 2023, tkad001, https://doi.org/10.1093/burnst/tkad001
DOI：

Wanchao Chen, Yang Wang, Jiancheng Zheng, Yan Chen, Can Zhang, Wei Yang, Lingling Wu, Zeyu Yang, Yu Wang, Chunmeng Shi, Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium, Burns & Trauma, Volume 11, 2023, tkad001, https://doi.org/10.1093/burnst/tkad001 DOI：

摘要

Abstract

BackgroundRadiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation. The most important feature of radiation ulcers is progressive ulceration

which results in the expansion of radiation injury to the nonirradiated area and refractory wounds. Current theories cannot explain the progression of radiation ulcers. Cellular senescence refers to as irreversible growth arrest that occurs after exposure to stress

which contributes to tissue dysfunction by inducing paracrine senescence

stem cell dysfunction and chronic inflammation. However

it is not yet clear how cellular senescence facilitates the continuous progression of radiation ulcers. Here

we aim to investigate the role of cellular senescence in promoting progressive radiation ulcers and indicate a potential therapeutic strategy for radiation ulcers.MethodsRadiation ulcer animal models were established by local exposure to 40 Gy X-ray radiation and continuously evaluated for >260 days. The roles of cellular senescence in the progression of radiation ulcers were assessed using pathological analysis

molecular detection and RNA sequencing. Then

the therapeutic effects of conditioned medium from human umbilical cord mesenchymal stem cells (uMSC-CM) were investigated in radiation ulcer models.ResultsRadiation ulcer animal models with features of clinical patients were established to investigate the primary mechanisms responsible for the progression of radiation ulcers. We have characterized cellular senescence as being closely associated with the progression of radiation ulcers and found that exogenous transplantation of senescent cells significantly aggravated them. Mechanistic studies and RNA sequencing suggested that radiation-induced senescent cell secretions were responsible for facilitating paracrine senescence and promoting the progression of radiation ulcers. Finally

we found that uMSC-CM was effective in mitigating the progression of radiation ulcers by inhibiting cellular senescence.ConclusionsOur findings not only characterize the roles of cellular senescence in the progression of radiation ulcers but also indicate the therapeutic potential of senescent cells in their treatment.

关键词

Keywords

Ionizing radiationRadiation ulcerCellular senescenceuMSC-CM

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