Zhong Hao, Zhou Mi, Guo Junrui, Chen Danyang, Xing Cong, Liu Song, Yang Hongjiang, Ma Hongpeng, Zhang Qi, Yang Jianhai, Feng Shiqing, Ning Guangzhi
International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300350, China.
Mater Today Bio. 2025 Apr 26;32:101805. doi: 10.1016/j.mtbio.2025.101805. eCollection 2025 Jun.
Spinal cord injury (SCI) is a devastating condition of the central nervous system, characterized by disrupted regulation of the immune microenvironment and the loss of electrical signaling, which poses significant challenges to repair. Neural stem cells (NSCs) have the potential to promote functional recovery after SCI; however, their therapeutic potential is limited by poor survival, restricted proliferation, and suboptimal differentiation. Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) possess powerful paracrine and immunomodulatory properties, providing a supportive niche that improves the engraftment and function of NSCs. Recently, piezoelectric materials have attracted increasing attention for their ability to convert mechanical energy into electrical signals, thus providing a noninvasive, wireless alternative to traditional electrode-based therapies for neural regeneration. In this study, we investigated the synergistic effects of NSCs and hUCMSCs, focusing on how hUCMSCs direct NSC differentiation and the mechanisms underlying this action. We also introduce an ultrasound-driven wireless piezoelectric hydrogel, which generates electrical signals through the piezoelectric effect. In vitro, wireless electrical stimulation activated primary cortical neurons, stimulated axonal growth, and promoted neuronal plasticity through the Piezo1 channel and downstream CREB/CAMKII signaling pathways. In a rat SCI model, wireless piezoelectric hydrogel synergized with cotransplanting NSCs-hUCMSCs and modulated the immune microenvironment during the acute phase, thereby restructuring scar cavities during the chronic phase, suppressing scar formation, accelerating neurogenesis, and facilitating axonal regeneration. These results emphasize the potential of synergizing stem cell therapies with wireless piezoelectric stimulation as a promising strategy for SCI repair, providing novel insights into the clinical translation of regenerative treatments.
脊髓损伤（SCI）是中枢神经系统的一种毁灭性疾病，其特征是免疫微环境调节紊乱和电信号丧失，这给修复带来了重大挑战。神经干细胞（NSCs）有促进脊髓损伤后功能恢复的潜力；然而，它们的治疗潜力受到存活率低、增殖受限和分化不理想的限制。人脐带间充质干细胞（hUCMSCs）具有强大的旁分泌和免疫调节特性，提供了一个支持性微环境，可改善神经干细胞的植入和功能。最近，压电材料因其将机械能转化为电信号的能力而受到越来越多的关注，从而为神经再生提供了一种非侵入性、无线的传统电极疗法替代方案。在本研究中，我们研究了神经干细胞和人脐带间充质干细胞的协同作用，重点关注人脐带间充质干细胞如何引导神经干细胞分化及其作用机制。我们还引入了一种超声驱动的无线压电流体凝胶，它通过压电效应产生电信号。在体外，无线电刺激激活了原代皮层神经元，刺激了轴突生长，并通过Piezo1通道和下游CREB/CAMKII信号通路促进了神经元可塑性。在大鼠脊髓损伤模型中，无线压电流体凝胶与共移植的神经干细胞-人脐带间充质干细胞协同作用，并在急性期调节免疫微环境，从而在慢性期重塑瘢痕腔，抑制瘢痕形成，加速神经发生，并促进轴突再生。这些结果强调了将干细胞疗法与无线压电刺激相结合作为脊髓损伤修复的一种有前景策略的潜力，为再生治疗的临床转化提供了新的见解。
