Warnecke Athanasia, Harre Jennifer, Staecker Hinrich, Prenzler Nils, Strunk Dirk, Couillard-Despres Sebastien, Romanelli Pasquale, Hollerweger Julia, Lassacher Teresa, Auer Daniela, Pachler Karin, Wietzorrek Georg, Köhl Ulrike, Lenarz Thomas, Schallmoser Katharina, Laner-Plamberger Sandra, Falk Christine S, Rohde Eva, Gimona Mario
Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Hannover, Germany.
Department of Otolaryngology, Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, Kansas.
Clin Transl Med. 2020 Dec;10(8):e262. doi: 10.1002/ctm2.262.
The lack of approved anti-inflammatory and neuroprotective therapies in otology has been acknowledged in the last decades and recent approaches are heralding a new era in the field. Extracellular vesicles (EVs) derived from human multipotent (mesenchymal) stromal cells (MSC) can be enriched in vesicular secretome fractions, which have been shown to exert effects (eg, neuroprotection and immunomodulation) of their parental cells. Hence, MSC-derived EVs may serve as novel drug candidates for several inner ear diseases. Here, we provide first evidence of a strong neuroprotective potential of human stromal cell-derived EVs on inner ear physiology. In vitro, MSC-EV preparations exerted immunomodulatory activity on T cells and microglial cells. Moreover, local application of MSC-EVs to the inner ear significantly attenuated hearing loss and protected auditory hair cells from noise-induced trauma in vivo. Thus, EVs derived from the vesicular secretome of human MSC may represent a next-generation biological drug that can exert protective therapeutic effects in a complex and nonregenerating organ like the inner ear.
在过去几十年中，耳科学领域一直缺乏经批准的抗炎和神经保护疗法，而最近的研究方法正在开创该领域的新纪元。源自人多能（间充质）基质细胞（MSC）的细胞外囊泡（EV）可富集于囊泡分泌组部分，这些部分已显示出发挥其亲代细胞的作用（如神经保护和免疫调节）。因此，MSC衍生的EV可能成为治疗多种内耳疾病的新型候选药物。在此，我们首次提供了人基质细胞衍生的EV对内耳生理具有强大神经保护潜力的证据。在体外，MSC-EV制剂对T细胞和小胶质细胞具有免疫调节活性。此外，将MSC-EV局部应用于内耳可显著减轻听力损失，并在体内保护听觉毛细胞免受噪声诱导的损伤。因此，源自人MSC囊泡分泌组的EV可能代表一种下一代生物药物，可在像内耳这样复杂且不可再生的器官中发挥保护性治疗作用。
