Bone marrow mesenchymal stem cells (BMSCs) are involved in cancer initiation and metastasis, and sometimes mediate cell communication by releasing exosomes and delivering microRNAs (miRNAs). The study aims to investigate the effects of exosomal hsa-miR-23b-3p derived from human BMSCs on intracranial aneurysm (IA). Firstly, human BMSCs-derived exosomes were extracted by ultra-high speed centrifugation. After clinical specimen collection, imbalance of T helper (Th) 17/Treg was found in patients with IA. Then, basilar artery aneurysm models were established and BMSCs-derived exosomes were isolated and identified. The results showed that BMSCs-derived exosomes improved pathological remodeling of IA wall, upregulated the contractile phenotype and inhibited the secretory phenotype of smooth muscle cells and reduced the number of Th17 cells to maintain the balance of Th17/Treg. In addition, human BMSCs-derived exosomes inhibited the activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NF-κB) signaling pathway and maintained Th17/Treg balance, which in turn interfered with aneurysm formation. Finally, the targeting relationship between hsa-miR-23b-3p and KLF5 was confirmed. We further noted that BMSCs-derived exosomal hsa-miR-23b-3p inhibited IA formation by targeting KLF5 through suppression of the PI3k/Akt/NF-κB signaling pathway. All in all, our study concluded that BMSCs-derived exosomal hsa-miR-23b-3p could maintain Th17/Treg balance by targeting KLF5 through suppression of the PI3k/Akt/NF-κB signaling pathway, thus inhibit IA formation.

骨髓间充质干细胞 (BMSCs) 参与癌症的发生和转移，有时通过释放外泌体和传递 microRNA (miRNAs) 来介导细胞通讯。该研究旨在研究源自人 BMSC 的外泌体 hsa-miR-23b-3p 对颅内动脉瘤 (IA) 的影响。首先，通过超高速离心提取人骨髓间充质干细胞来源的外泌体。临床标本采集后发现IA患者T辅助（Th）17/Treg失衡。然后，建立基底动脉瘤模型并分离和鉴定骨髓间充质干细胞来源的外泌体。结果表明，BMSCs 来源的外泌体改善了 IA 壁的病理重塑，上调收缩表型并抑制平滑肌细胞的分泌表型并减少 Th17 细胞数量以维持 Th17/Treg 的平衡。此外，人骨髓间充质干细胞衍生的外泌体抑制磷脂酰肌醇 3 激酶 (PI3K)/蛋白激酶 B (Akt)/核因子-κB (NF-κB) 信号通路的激活并维持 Th17/Treg 平衡，进而干扰动脉瘤的形成。最后，证实了hsa-miR-23b-3p与KLF5之间的靶向关系。我们进一步注意到，BMSCs 衍生的外泌体 hsa-miR-23b-3p 通过抑制 PI3k/Akt/NF-κB 信号通路靶向 KLF5 来抑制 IA 形成。总而言之，