Wang Yingshuai, Yu Tao, Hu Feihu
School of Lifescience and Technology, Weifang Medical University, Weifang, China.
Front Bioeng Biotechnol. 2022 Feb 8;10:825146. doi: 10.3389/fbioe.2022.825146. eCollection 2022.
Therapeutic strategies of microRNAs (miRNAs) and exosomes have been systematically explored as an enhancing application by paracrine and modulating cellular activity after internalization of recipient cells , and progressively developed to meet the requirements of peripheral nerve regeneration . However, how to obtain exosomes with superior properties and effectively deliver miRNAs becomes a key challenge. Hypocapnia environment might play unexpected outcomes in strengthening exosome function when culturing adipose-derived stem cells (ASCs). Previously, we discovered the intensive regulation of miR-218 on the differentiation of ASCs. In the present study, we analyzed the functional differences of secreted exosomes in response to hypocapnia stimulation, and explored the application in combination with miR-218 to facilitate sciatic nerve regeneration. Our results indicated that the delivery system of engineered exosomes derived from ASCs remarkably loads upregulated miR-218 and promotes cellular activity in the recipient cells (PC12 cells), and hypocapnia stimuli-responsive exosomes exhibit strengthening properties. Furthermore, in a sciatic nerve injury model, exosomes delivering miR-218 combined with engineered scaffold facilitated the regeneration of injured sciatic nerves. In the hypocapnia-stimulated exosome group, more encouraging promotion was revealed on the regeneration of motor and nerve fibers. Hypoc-miR-218-ASC exosomes are suggested as a promising cell-free strategy for peripheral nerve repair.
微小RNA（miRNA）和外泌体的治疗策略已被系统地探索，作为一种通过旁分泌增强应用，并在受体细胞内化后调节细胞活性，且逐渐发展以满足周围神经再生的需求。然而，如何获得具有优异特性的外泌体并有效递送miRNA成为一个关键挑战。低碳酸血症环境在培养脂肪干细胞（ASC）时可能在增强外泌体功能方面产生意想不到的结果。此前，我们发现了miR-218对ASC分化的强烈调控作用。在本研究中，我们分析了低碳酸血症刺激下分泌的外泌体的功能差异，并探索了其与miR-218联合应用以促进坐骨神经再生。我们的结果表明，源自ASC的工程化外泌体递送系统显著上调miR-218的负载量，并促进受体细胞（PC12细胞）的细胞活性，且低碳酸血症刺激响应性外泌体表现出增强特性。此外，在坐骨神经损伤模型中，递送miR-218的外泌体与工程化支架相结合促进了受损坐骨神经的再生。在低碳酸血症刺激的外泌体组中，在运动和神经纤维再生方面显示出更令人鼓舞的促进作用。低碳酸血症刺激的miR-218-ASC外泌体被认为是一种有前景的用于周围神经修复的无细胞策略。
