Abstract
Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the repair of brain function in central nervous system (CNS) diseases. Radial extracorporeal shock wave therapy (rESWT) is a non-invasive and innovative treatment for many conditions, yet little is known about the effects of this treatment on NSCs. Mouse NSCs (NE-4C) were exposed to rESWT with 1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 bar (500 impulses, and 2 Hz) in vitro. Cell viability test results indicated that rESWT, at a dose of 2.5 bar, 500 impulses, and 2 Hz, increased NE-4C viability within 72 h, and that the PI3K/AKT pathway was involved in its mechanisms. Exposure to rESWT also affected proliferation and differentiation of NE-4C after 8 weeks, which may be associated with Wnt/β-catenin and Notch pathways. This assessment is corroborated by the ability of inhibitors of Wnt/β-catenin [Dickkopf-1 (Dkk-1)] and the Notch pathway (DAPT) to weaken proliferation and differentiation of NSCs. In summary, a proper dose of rESWT enhanced NSCs augment via the PI3K/AKT pathway initially. Also, Wnt/β-catenin and the Notch pathway play important roles in regulation of the long-term efficacy of rESWT. This study reveals a novel approach to culture NSCs in vitro and support neurogenesis.
Highlights
Many researchers have studied the characteristics and regulatory mechanisms of Neural stem cell (NSC) to better culture NSCs
The results of the current study demonstrate that radial extracorporeal shock wave therapy (ESWT) (rESWT) promoted the proliferation and differentiation of mouse NSCs in vitro
As the second generation of focused ESWT (fESWT), with waves dispersing eccentrically from the applicator tip[31], rESWT is a breakthrough in clinical medicine because of its better security than fESWT, its simplicity of use, and especially for its excellent therapeutic results[32]; for example, rESWT simplifies application without anesthesia or image-guided location and lessens risks by reflecting the pathology zone[32]
Summary
Many researchers have studied the characteristics and regulatory mechanisms of NSCs to better culture NSCs. The proliferation and final fate of NSCs depend on the activation of growth factors and specific signaling pathways, such as PI3K (phosphatidylinositol 3-kinase)/AKT11, Wnt/β-catenin[12], and Notch signaling[13]. Notch signaling is a novel pathway that influences many aspects of NSCs18; for examples, Notch signaling is important in the proliferation and fate of NSCs by maintaining the self-renewable state of NSCs, both in vivo and in vitro[19], and plays an essential role in differentiation to neurons[20]. We used NE-4C mouse NSCs to assess the effect by rESWT on proliferation and differentiation and to further explore the possible signaling pathway of PI3K/AKT, Wnt/β-catenin, and Notch signaling in vitro
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