Long-term selective stimulation of transplanted neural stem/progenitor cells for spinal cord injury improves locomotor function
Long-term selective stimulation of transplanted neural stem/progenitor cells for spinal cord injury improves locomotor function
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DOI：
10.1016/j.celrep.2021.110019
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发表时间：
2021-11-23
期刊：
影响因子：
8.8
通讯作者：
Okano, Hideyuki
中科院分区：
文献类型：
--
作者：
Kawai, Momotaro;Imaizumi, Kent;Okano, Hideyuki
在脊髓损伤（SCI）的细胞移植治疗中，移植的人诱导多能干细胞衍生的神经干/祖细胞（hiPSC-NS/PC）主要分化为神经元，在类似于神经发育的过程中形成突触。在发育中的神经系统中，未成熟神经元的活动在构建和维持新的突触中具有重要作用。因此，我们研究了增强移植的hiPSC-NS/PC的活性如何影响移植细胞本身和宿主组织。我们发现，hiPSC衍生的神经细胞的化学发生刺激增强了细胞活性和体外神经元与神经元的相互作用。在SCI的啮齿动物模型中，移植的hiPSC-NS/PC的连续和选择性化学遗传学刺激也增强了周围宿主组织中突触相关基因和蛋白质的表达，并防止受损脊髓萎缩，从而改善运动功能。这些发现为增强移植物内的活性以提高细胞移植治疗SCI的疗效提供了策略。
In cell transplantation therapy for spinal cord injury (SCI), grafted human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) mainly differentiate into neurons, forming synapses in a process similar to neurodevelopment. In the developing nervous system, the activity of immature neurons has an important role in constructing and maintaining new synapses. Thus, we investigate how enhancing the activity of transplanted hiPSC-NS/PCs affects both the transplanted cells themselves and the host tissue. We find that chemogenetic stimulation of hiPSC-derived neural cells enhances cell activity and neuron-to-neuron interactions in vitro. In a rodent model of SCI, consecutive and selective chemogenetic stimulation of transplanted hiPSC-NS/PCs also enhances the expression of synapse-related genes and proteins in surrounding host tissues and prevents atrophy of the injured spinal cord, thereby improving locomotor function. These findings provide a strategy for enhancing activity within the graft to improve the efficacy of cell transplantation therapy for SCI.