Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury
Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury
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DOI：
10.1016/j.stem.2016.08.020
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发表时间：
2016-10-06
期刊：
影响因子：
23.9
通讯作者：
Kriegstein, Arnold R.
中科院分区：
文献类型：
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作者：
Fandel, Thomas M.;Trivedi, Alpa;Kriegstein, Arnold R.
神经性疼痛和膀胱功能障碍是许多脊髓损伤患者的重要生活质量问题。受损脊髓中GABA能张力的丧失可能导致这些症状的出现。先前的研究表明，从内侧神经节隆起（MGE）移植啮齿动物抑制性中间神经元前体增强脑和脊髓中的GABA能信号传导。在这里，我们看看是否移植MGE样细胞来自人胚胎干细胞（hESC-MGE）可以减轻脊髓损伤的病理影响。我们发现，移植到损伤的小鼠脊髓6个月后，hESC-MGE分化为GABA能神经元亚型，并接受突触输入，表明功能整合到宿主脊髓。此外，移植的动物表现出改善的膀胱功能和减轻疼痛相关症状。因此，我们的研究结果表明，这种方法可能是一种有价值的策略，以改善脊髓损伤的不良反应。
Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury.