en Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;"><span style="font-size:10pt"><span style="text-justify:newspaper"><span style="text-kashida-space:50%"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Background:</span></span></span></span></span></span> <span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-GB">Radiotherapy, while primarily used in oncology, can induce significant cellular stress in non-target tissues, including hypoxia-like conditions, oxidative damage, and impaired cell function. Trophoblast cell lines exposed to X-ray irradiation exhibit suppressed proliferation, migration, and invasion-phenomena that closely mimic trophoblast dysfunction under placental stress and radioresistance mechanisms in tumor cells. This study aimed to investigate the protective mechanism of Mesenchymal stem cell-derived exosomes (MSCs-Exos) on X-ray irradiated HTR-8/SVneo trophoblast cells, focusing on restoration of proliferation, migration, and invasion capacities through activation of the PI3K/AKT signaling pathway. </span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-GB">Materials and Methods: </span></span></span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-GB">HTR-8/SVneo cells were subjected to 6 Gy X-ray irradiation to establish a radiation-injury model. Experimental groups included: normal control (CG), irradiation model (MG), exosome intervention (EG; 100 </span></span></span></span><span lang="el" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:el">&mu;</span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">g/mL MSCs-Exos post-irradiation), and PI3K inhibitor (IG; LY294002 + MSCs-Exos). Cell proliferation (CCK-8), migration and invasion (Transwell), PI3K/AKT pathway activation (Western blot), inflammatory cytokines (ELISA), and oxidative stress markers (ROS, MDA, SOD) were evaluated. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Results: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">X-ray irradiation significantly impaired proliferation, migration, and invasion while downregulating p-PI3K and p-AKT expression and increasing inflammatory cytokines and oxidative stress (all P < 0.001). MSCs-Exos treatment markedly reversed these effects, restoring functional capacities, reactivating PI3K/AKT, and alleviating inflammation and oxidative damage. These benefits were attenuated by LY294002. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Conclusion: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">MSCs-Exos protect X-ray-irradiated trophoblast cells against radiation-induced injury by activating the PI3K/AKT pathway. The findings highlight a novel radioprotective role of MSCs-Exos and provide mechanistic insights applicable to radiation-induced placental injury models and tumor radioresistance.</span></span></span></span></span></span></span></span></span></span></div> Exosomes, mesenchymal stem cells, trophoblasts, ionizing radiation, PI3K/AKT pathway, radiation protection. 495 500 http://ijrr.com/browse.php?a_code=A-10-1-1522&slc_lang=en&sid=1 H. Liu liuhuimin1221@163.com 7900319475328460033612 7900319475328460033612 Yes Department of Obstetrical, Beidahuang Industry Group General Hospital, Harbin 150000, Heilongjiang Province, China L. Tan 3871557671@qq.com 7900319475328460033613 7900319475328460033613 No Department of Obstetrical, Beidahuang Industry Group General Hospital, Harbin 150000, Heilongjiang Province, China