School of Biological Science and Medical Engineering, Beihang University, Hai Dian District 100191, Beijing, China.
Exp Biol Med (Maywood). 2013 Aug 1;238(8):951-9. doi: 10.1177/1535370213494635.
Stem cell therapy may provide a therapeutic method for the replacement and regeneration of damaged neurons of the central nervous system. However, neural stem cells (NSCs) and neural precursor cells (NPCs) are especially vulnerable after transplantation due to a lack of sufficient growth factors at the transplant site. Electrical stimulation (ES) has recently been found to participate in the regulation of cell proliferation, growth, differentiation, and migration, but its underlying anti-apoptotic effects remain unclear. This study investigated the protective effects of biphasic electrical stimulation (BES) on olfactory bulb NPCs against growth factor-deprived apoptosis, examining the survival and apoptotic features of the cells. Differentiation was assessed by neuronal and glial markers. Brain-derived neurotrophic factor-phosphatidylinositol 3'-kinase (BDNF)-PI3K/Akt pathway activation was determined by enzyme-linked immunosorbent assay and Western blot. The chemical inhibitor wortmannin was used to inhibit the PI3K/Akt pathway. BES exerts a protective effect against growth factor-deprived apoptosis in the NPCs. BES enhanced cell survival and decreased the apoptotic/necrotic rate. Expression of phosphorylated Akt and BDNF secretion increased with BES for 12 h. Furthermore, the protective effects of BES were inhibited by blocking PI3K/AKT signalling. These results suggest that BES prevents growth factor-deprived apoptosis through the BDNF-PI3K/Akt signalling. This work strengthens the opinion that BES may be used as an auxiliary strategy for improving cell survival and preventing cell apoptosis in stem cell-based transplantation therapy.
干细胞治疗可能为中枢神经系统受损神经元的替代和再生提供一种治疗方法。然而，神经干细胞（NSCs）和神经前体细胞（NPCs）在移植后由于移植部位缺乏足够的生长因子而特别脆弱。最近发现电刺激（ES）参与细胞增殖、生长、分化和迁移的调节，但其潜在的抗细胞凋亡作用尚不清楚。本研究探讨了双相电刺激（BES）对嗅球 NPC 对抗生长因子剥夺性细胞凋亡的保护作用，研究了细胞的存活和凋亡特征。通过神经元和神经胶质标志物评估分化。通过酶联免疫吸附试验和 Western blot 测定脑源性神经营养因子-磷酸肌醇 3-激酶（BDNF）-PI3K/Akt 通路的激活。使用化学抑制剂 wortmannin 抑制 PI3K/Akt 通路。BES 对 NPC 中的生长因子剥夺性细胞凋亡具有保护作用。BES 增强了细胞的存活并降低了凋亡/坏死率。用 BES 处理 12 小时后，磷酸化 Akt 的表达和 BDNF 的分泌增加。此外，BES 的保护作用通过阻断 PI3K/AKT 信号通路而受到抑制。这些结果表明，BES 通过 BDNF-PI3K/Akt 信号通路防止生长因子剥夺性细胞凋亡。这项工作加强了这样一种观点，即 BES 可以用作一种辅助策略，用于提高基于干细胞的移植治疗中细胞的存活和防止细胞凋亡。
