Transplanted neural stem cells promote neural tissue regeneration and functional recovery primarily by releasing paracrine factors. Exosomes act as important secreted paracrine molecules to deliver therapeutic agents involved in cellular functions. Here, we focused on the role of exosomes (hNSC-Exo) derived from human neural stem cells (hNSCs). We utilized the pro-inflammatory factor interferon gamma (IFN-γ) to induce the generation of altered exosomes (IFN-γ-hNSC-Exo), and compared their roles with those of hNSC-Exo and explored the potential mechanism. Importantly, IFN-γ preconditioning did not affect the secretion, but significantly altered the ability of exosomes derived from hNSCs. Moreover, IFN-γ-hNSC-Exo was functionally superior to hNSC-Exo; showed increased cell proliferation and cell survival and decreased cell apoptosis in vitro. Furthermore, IFN-γ-hNSC-Exo further exerted therapeutic effects (showed better behavioral and structural outcomes) compared to those of hNSCs-Exo in an ischemic stroke rat model. Next-generation sequencing (NGS) revealed specific exosomal miRNAs (hsa-miR-206, hsa-miR-133a-3p and hsa-miR-3656) in IFN-γ-hNSC-Exo with important roles in cell survival. Thus, our findings demonstrate that the inflammatory factor IFN-γ can regulate the functions of exosomes and highlight its role in regulating the application of neural stem cell-derived exosomes.

移植的神经干细胞主要通过释放旁分泌因子来促进神经组织再生和功能恢复。外泌体充当重要的分泌旁分泌分子，以传递参与细胞功能的治疗剂。在这里，我们集中于人类神经干细胞（hNSCs）衍生的外来体（hNSC-Exo）的作用。我们利用促炎因子干扰素γ（IFN-γ）诱导了外泌体（IFN-γ-hNSC-Exo）的产生，并将它们与hNSC-Exo的作用进行了比较，并探讨了其潜在机制。重要的是，IFN-γ预处理不会影响分泌，但会显着改变源自hNSC的外泌体的能力。此外，IFN-γ-hNSC-Exo在功能上优于hNSC-Exo。显示细胞增殖和细胞存活增加，细胞凋亡减少体外。此外，在缺血性中风大鼠模型中，与hNSCs-Exo相比，IFN-γ-hNSC-Exo进一步发挥了治疗作用（表现出更好的行为和结构结果）。下一代测序（NGS）揭示了IFN-γ-hNSC-Exo中特定的外泌体miRNA（hsa-miR-206，hsa-miR-133a-3p和hsa-miR-3656）在细胞存活中具有重要作用。因此，我们的发现表明，炎性因子IFN-γ可以调节外泌体的功能，并突出其在调节神经干细胞来源的外泌体应用中的作用。