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

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

机构地区：[1]Institute of Rocket Force Medicine,State Key Laboratory of Trauma,Burns and Combined Injury,Third Military Med-ical University(Army Medical University),400038,Chongqing,China [2]Breast and Thyroid Surgical Department,Chongqing General Hospital,401147,Chongqing,China

出　　处：《Burns & Trauma》2023年第1期203-216,共14页烧伤与创伤（英文）

基　　金：supported by the Key Program of the National Natural Science Foundation of China(82030056);the Intramural Research Project Grants(2021-JCJQ-ZD-077-11,AWS17J007 and 2018-JCJQ-ZQ-001);Postdoctoral Innovative Talent Support Program in Chongqing(CQBX2021010).

摘　　要：Background:Radiation 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 irre-versible 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.Methods:Radiation 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.Results:Radiation 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.Conclusions:Our findings not only characterize

关 键 词：Ionizing radiation Radiation ulcer Cellular senescence uMSC-CM 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]