Bmi1 regulates neural differentiation of mesenchymal stem cells through the Wnt3a‑RhoA signaling pathway to repair ischemic brain injury in rats

作者：Kunling Chen, Hongjie Zhou, Jie Zhang, Yiwei Zhang, Xiaobing Dou, Qin Yu, Liping Zhou · 发表于：International Journal of Molecular Medicine · 年份：2025 · DOI：10.3892/ijmm.2025.5596 · 被引用次数：3 · 研究领域：Neurogenesis and neuroplasticity mechanisms、Pluripotent Stem Cells Research、Epigenetics and DNA Methylation

Ischemic brain injury (IBI) is characterized by high morbidity, disability and mortality rates; however, it lacks effective clinical treatments. Mesenchymal stem cells (MSCs), as pluripotent stem cells with self‑renewal capacity and multilineage differentiation potential, have emerged as a promising therapeutic strategy for neurological disorders. In the present study, in vitro experiments were performed using the Wnt signaling agonist Wnt3a and the B lymphoma Mo‑MLV insertion region 1 homolog (Bmi1) small molecule inhibitor PTC209 to treat MSCs, and the roles and regulatory mechanisms of the Bmi1 and Wnt3a‑RhoA signaling pathways on the neural differentiation of MSCs were explored by MTT assay, immunofluorescence analysis and western blotting. In vivo experiments were also performed by establishing a rat model of middle cerebral artery occlusion (MCAO), transplanting different MSCs into the rat brain tissues after in vitro labeling, and comparing ischemic brain damage in each group of rats by Neurological Severity Score scoring, grasp assay, triphenyltetrazolium chloride staining, hematoxylin and eosin staining, and assessing neurological recovery via immunofluorescence and western blot analysis. The in vivo study aimed to assess the roles of the Bmi1 and Wnt3a‑RhoA signaling pathways in brain injury repair in MCAO rats and the mechanism. Specifically, recombinant Wnt3a cytokine was administered to upregulate the Wnt3a‑RhoA pathway, whereas the small‑molecule inhibit...