The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.

中文翻译：

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人诱导多能干细胞源性神经干/祖细胞体外基因治疗与突触组织者 CPTX 治疗脊髓损伤

来自人类诱导多能干细胞 (hiPSC) 的神经干/祖细胞 (NS/PC) 的移植在脊髓损伤 (SCI) 模型动物中显示出了前景。在移植神经元和宿主神经元之间建立功能性突触连接对于运动功能恢复至关重要。为了提高治疗效果，我们开发了一种基因疗法，旨在通过在 hiPSC-NS/PC 中表达合成的兴奋性突触组织者 CPTX 来促进突触形成。使用免疫受损的 SCI 转基因大鼠模型，我们通过组织学和功能分析评估了移植表达 CPTX 的 hiPSC-NS/PC 的效果。我们的研究结果显示移植部位的兴奋性突触形成显着增加。逆行单突触追踪表明，CPTX 促进了移植神经元广泛整合到周围神经元束中。因此，运动和脊髓传导显着改善。因此，针对突触形成的基因治疗有望在未来的临床应用中发挥作用，并为 SCI 患者带来潜在的益处。