肿瘤细胞治疗研究
英文原题：Regenerative effects of myogenic gene transfected MSC derived exosomes on radiation esophagitis.
转染生肌基因的MSC来源外泌体可显著促进放射诱导损伤后的食管肌肉再生并减轻纤维化。这种无细胞治疗方法有望成为一种新颖且实用的策略，用于应对接受头颈部恶性肿瘤放疗患者的放射性食管炎。
放射性食管炎是头颈部肿瘤放疗的常见不良反应，其特征为食管肌组织的不可逆损伤和纤维化。尽管间充质干细胞（MSC）治疗正逐渐成为一种有前景的组织再生手段，但由于细胞在体内的活力与分化问题，其临床转化仍面临挑战。本研究利用放射性食管纤维化小鼠模型，评估转染生肌基因（MyoD、Myogenin、Myf6，简称 Myo-MIX）的 MSC 来源外泌体的再生疗效。
人脂肪来源的MSC通过电穿孔转染Myo-MIX质粒，并使用ExoQuick从条件培养基中收集外泌体。采用纳米颗粒跟踪分析和透射电子显微镜对外泌体的大小和形态进行表征。建立小鼠局部放射性食管损伤模型（10 Gy，2次分割），随后经肌内注射Myo-MIX外泌体。通过Masson三色染色、免疫组化（-SMA、Calponin、CD68）和定量RT-PCR检测再生和抗纤维化结局。
与 PBS 处理的对照组和 naïve MSC-exosome 组相比，Myo-MIX 外泌体治疗使纤维化和炎症反应显著减少。观察到肌肉结构恢复增强，并伴有 Calponin 和 -SMA 表达升高，以及 CD68+ 巨噬细胞浸润减少。基因表达谱分析表明，Myo-MIX 外泌体治疗组中肌源性标志物和抗纤维化标志物水平升高。
BACKGROUND: Radiation esophagitis is a common adverse effect of radiotherapy for head and neck cancers, and is marked by irreversible damage and fibrosis of esophageal muscle tissue. Although mesenchymal stem cell (MSC) therapy is emerging as a promising approach for tissue regeneration, clinical translation remains challenging due to issues with cell viability and differentiation in vivo. This study evaluates the regenerative efficacy of exosomes derived from MSCs transfected with myogenic genes (MyoD, Myogenin, Myf6, referred to as Myo-MIX) using a murine model of radiation-induced esophageal fibrosis. METHODS: Human adipose-derived MSCs were transfected with Myo-MIX plasmids by electroporation, and exosomes were collected from conditioned media using ExoQuick. Nanoparticle tracking analysis and transmission electron microscopy were employed to characterize exosomal size and morphology. A mouse model of localized radiation-induced esophageal injury (10 Gy 2 fractions) was generated and followed by intramuscular administration of Myo-MIX exosomes. Regenerative and anti-fibrotic outcomes were examined through Masson's trichrome staining, immunohistochemistry ( -SMA, Calponin, CD68), and quantitative RT-PCR. RESULTS: Treatment with Myo-MIX exosomes resulted in a pronounced decrease in fibrosis and inflammatory response compared to PBS-treated controls and na ve MSC-exosome groups. Enhanced restoration of muscular architecture was observed, accompanied by elevated expression of Calponin and -SMA, and a reduction in CD68 + macrophage infiltration. Gene expression profiling indicated increased levels of myogenic and anti-fibrotic markers in the Myo-MIX exosome-treated group. CONCLUSION: Exosomes from myogenic gene-transfected MSCs significantly enhance esophageal muscle regeneration and attenuate fibrosis after radiation-induced damage. This cell-free therapeutic approach holds potential as a novel and practical strategy for addressing radiation esophagitis in patients receiving radiotherapy for head and neck malignancies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
