Accelerated differentiation of human induced pluripotent stem cells into regionally specific dorsal and ventral spinal neural progenitor cells for application in spinal cord therapeutics.

Accelerated differentiation of human induced pluripotent stem cells into regionally specific dorsal and ventral spinal neural progenitor cells for application in spinal cord therapeutics.
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DOI:
10.3389/fnins.2023.1251906
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发表时间:
2023
影响因子:
4.3
通讯作者:
Parr, Ann M.
Parr, Ann M.
中科院分区:
医学2区
文献类型:
--
作者:
Huntemer-Silveira, Anne;Malone, Dane;Frie, Anna;Walsh, Patrick;Parr, Ann M.

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脊髓损伤可以削弱运动和感觉功能,完全恢复的可能性极小。近年来,利用人诱导多能干细胞(hiPSC)衍生的脊髓细胞类型用于脊髓损伤后的体内重塑和神经调节的研究大幅增长。然而,大多数用于脊髓神经元分化的方案是冗长的,缺乏适当的背腹侧或吻尾侧规范,并且通常不能在一个以上的细胞系中复制。此外,大多数研究人员目前利用hiPSC衍生的运动神经元用于损伤后的细胞移植,很少探索脊髓感觉神经元移植。缺乏利用感觉群体的研究可能部分是由于背角分化方案的相对稀缺。基于我们先前发表的工作,证明了从hiPSC快速建立原始外胚层群体,我们在这里描述了腹侧脊髓和背角祖细胞的多样化群体的产生。我们的工作创建了一个新的系统,允许背侧和腹侧脊髓神经元从相同的中间外胚层群体分化,使其有可能构建脊髓的背侧和腹侧域,同时降低变异性。这项技术可以与生物材料和药理学结合使用,以改善脊髓损伤的细胞移植,增加神经再生的潜力。
Spinal cord injury can attenuate both motor and sensory function with minimal potential for full recovery. Research utilizing human induced pluripotent stem cell (hiPSC) -derived spinal cell types for in vivo remodeling and neuromodulation after spinal cord injury has grown substantially in recent years. However, the majority of protocols for the differentiation of spinal neurons are lengthy, lack the appropriate dorsoventral or rostrocaudal specification, and are not typically replicated in more than one cell line. Furthermore, most researchers currently utilize hiPSC-derived motor neurons for cell transplantation after injury, with very little exploration of spinal sensory neuron transplantation. The lack of studies that utilize sensory populations may be due in part to the relative scarcity of dorsal horn differentiation protocols. Building upon our previously published work that demonstrated the rapid establishment of a primitive ectoderm population from hiPSCs, we describe here the production of a diverse population of both ventral spinal and dorsal horn progenitor cells. Our work creates a novel system allowing dorsal and ventral spinal neurons to be differentiated from the same intermediate ectoderm population, making it possible to construct the dorsal and ventral domains of the spinal cord while decreasing variability. This technology can be used in tandem with biomaterials and pharmacology to improve cell transplantation for spinal cord injury, increasing the potential for neuroregeneration.
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