Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Stem Cell Res Ther. 2023 Apr 15;14(1):88. doi: 10.1186/s13287-023-03314-7.
Mesenchymal stem cell (MSC) transplantation is a promising therapeutic approach for noise-induced hearing loss (NIHL). As the indispensable role of apoptosis in MSC transplantation was raised, the benefits of MSC-derived apoptotic vesicles (apoVs) in several disease models have been proved. However, whether apoVs benefit in NIHL have not been studied yet.
Female CBA/J mice and HEI-OC1 cells were used in this study. Flow cytometry, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were used to characterize apoVs. Proteomic analysis was used to identify function proteins in apoVs. Immunofluorescence was used to reveal distribution pattern. Auditory brainstem response (ABR) test was used to measure the effect of apoVs treatment. DCFH-DA staining and MitoSOX staining were used to indicate oxidative damage. Western-blot and qRT-PCR were used to study the signaling pathways.
We found that apoVs can be endocytosed by hair cells through systemic administration. Importantly, apoVs administration effectively attenuated NIHL and reduced hair cell loss by resisting oxidative damage in vivo. Further, apoVs application activated forkhead box o3 (FOXO3a)-mitochondrial superoxide dismutase 2(SOD2) pathway, which may relate to signal transduction and activators of transcription 3 (STAT3) in apoVs.
These findings uncovered the role of apoVs in preventing NIHL and resisting oxidative damage, indicating that apoVs is a promising way for inner ear delivery and a prospective cell-free therapy for NIHL.
间充质干细胞（MSC）移植是治疗噪声性听力损失（NIHL）的一种有前途的治疗方法。由于细胞凋亡在 MSC 移植中的作用不可或缺，MSC 来源的凋亡小体（apoVs）在几种疾病模型中的益处已得到证实。然而，apoVs 是否对 NIHL 有益尚未得到研究。
本研究使用雌性 CBA/J 小鼠和 HEI-OC1 细胞。流式细胞术、纳米颗粒跟踪分析（NTA）和透射电子显微镜（TEM）用于表征 apoVs。蛋白质组学分析用于鉴定 apoVs 中的功能蛋白。免疫荧光用于揭示分布模式。听觉脑干反应（ABR）测试用于测量 apoVs 处理的效果。DCFH-DA 染色和 MitoSOX 染色用于指示氧化损伤。Western-blot 和 qRT-PCR 用于研究信号通路。
我们发现 apoVs 可以通过全身给药被毛细胞内吞。重要的是，apoVs 给药通过在体内抵抗氧化损伤有效减轻了 NIHL 并减少了毛细胞损失。此外，apoVs 应用激活了叉头框 O3（FOXO3a）-线粒体超氧化物歧化酶 2（SOD2）途径，这可能与 apoVs 中的信号转导和转录激活因子 3（STAT3）有关。
这些发现揭示了 apoVs 在预防 NIHL 和抵抗氧化损伤中的作用，表明 apoVs 是一种有前途的内耳递药方式，也是治疗 NIHL 的有前景的无细胞治疗方法。
