J Biomed Nanotechnol. 2021 Jan 1;17(1):100-114. doi: 10.1166/jbn.2021.3008.
Ionizing radiation (IR) therapy for malignant tumors can damage adjacent tissues, leading to severe wound complications. Plasma-derived exosome treatment has recently emerged as a safe and impactful cell-free therapy. Herein, we aimed to determine whether plasma-derived exosomes could improve the healing of post-radiation wound. Rat plasma-derived exosomes (RP-Exos) were locally injected on cutaneous wounds created on the backs of irradiated rats and boosted the healing process as well as the deposition and remodeling of the extracellular matrix with collagen formation. Subsequently, the effects of RP-Exos were further evaluated on irradiated fibroblasts . The results suggested that exosomes promoted fibroblast proliferation, migration, cell cycle progression, and cell survival. Moreover, transcriptome sequencing analysis and quantitative polymerase chain reaction validation were performed to identify potential mechanisms. RPExos enhanced the expression of cell proliferation and radioresistance-related genes, and yet downregulated ferroptosis pathway in irradiated fibroblasts. Inhibition of ferroptosis by RP-Exos was further confirmed through colorimetric assay, fluorescence probe and flow cytometry in ferroptosis-induced fibroblasts. Our results suggest that RP-Exos regulate cell proliferation and ferroptosis in irradiated fibroblasts, thereby boosting the healing of irradiated wound. These findings support plasma-derived exosomes as a potential therapeutic method for post-radiation wound complications.
电离辐射（IR）治疗恶性肿瘤会损伤相邻组织，导致严重的伤口并发症。等离子体衍生的外泌体治疗最近作为一种安全且有效的无细胞治疗方法出现。在此，我们旨在确定等离子体衍生的外泌体是否可以改善放射性伤口的愈合。局部注射大鼠血浆衍生的外泌体（RP-Exos）于照射大鼠背部的皮肤伤口上，可促进愈合过程以及细胞外基质的沉积和重塑，形成胶原蛋白。随后，进一步评估了 RP-Exos 对辐照成纤维细胞的影响。结果表明，外泌体促进成纤维细胞的增殖、迁移、细胞周期进程和细胞存活。此外，进行了转录组测序分析和定量聚合酶链反应验证以确定潜在机制。RPExos 增强了与细胞增殖和放射抗性相关的基因的表达，而在辐照成纤维细胞中下调了铁死亡途径。通过铁死亡诱导的成纤维细胞中的比色测定、荧光探针和流式细胞术进一步证实了 RP-Exos 对铁死亡的抑制作用。我们的结果表明，RP-Exos 调节辐照成纤维细胞中的细胞增殖和铁死亡，从而促进辐照伤口的愈合。这些发现支持等离子体衍生的外泌体作为放射性伤口并发症的潜在治疗方法。
