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首页> 外文期刊>Stem cell research >Spinal cord organogenesis model reveals role of Flk1+ cells in self-organization of neural progenitor cells into complex spinal cord tissue - ScienceDirect
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Spinal cord organogenesis model reveals role of Flk1+ cells in self-organization of neural progenitor cells into complex spinal cord tissue - ScienceDirect

机译：脊髓器官发生模型揭示Flk1 +细胞在神经祖细胞自组织成复杂脊髓组织中的作用-ScienceDirect

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摘要

A platform for studying spinal cord organogenesis in vivo where embryonic stem cell (ESC)-derived neural progenitor cells (NPC) self-organize into spinal cord-like tissue after transplantation in subarachnoid space of the spinal cord has been described. We advance the applicability of this platform by imaging in vivo the formed graft through T2w magnetic resonance imaging (MRI). Furthermore, we used diffusion tensor imaging (DTI) to verify the stereotypical organization of the graft showing that it mimics the host spinal cord. Within the graft white matter (WM) we identified astrocytes that form glial limitans, myelinating oligodendrocytes, and myelinated axons with paranodes. Within the graft grey matter (GM) we identified cholinergic, glutamatergic, serotonergic and dopaminergic neurons. Furthermore, we demonstrate the presence of ESC-derived complex vasculature that includes the presence of blood brain barrier. In addition to the formation of mature spinal cord tissue, we describe factors that drive this process. Specifically, we identify Flk1+ cells as necessary for spinal cord formation, and synaptic connectivity with the host spinal cord and formation of host-graft chimeric vasculature as contributing factors. This model can be used to study spinal cord organogenesis, and as an in vivo drug discovery platform for screening potential therapeutic compounds and their toxicity.
机译：已经描述了用于研究体内脊髓器官发生的平台，其中胚胎干细胞（ESC）衍生的神经祖细胞（NPC）移植到脊髓的蛛网膜下腔后会自组织成脊髓样组织。我们通过T2w磁共振成像（MRI）对体内形成的移植物进行成像，从而提高了该平台的适用性。此外，我们使用扩散张量成像（DTI）来验证移植物的定型结构，表明其模仿宿主脊髓。在移植物白质（WM）中，我们鉴定出星形胶质细胞形成神经胶质局限性，髓鞘少突胶质细胞和髓旁轴突的髓鞘轴突。在移植物灰质（GM）中，我们鉴定出胆碱能，谷氨酸能，血清素能和多巴胺能神经元。此外，我们证明了ESC衍生的复杂脉管系统的存在，其中包括血脑屏障的存在。除了形成成熟的脊髓组织外，我们还描述了驱动这一过程的因素。具体来说，我们确定Flk1 +细胞是脊髓形成所必需的，并且与宿主脊髓的突触连接以及宿主移植嵌合脉管系统的形成是促成因素。该模型可用于研究脊髓器官发生，并用作筛选潜在治疗化合物及其毒性的体内药物发现平台。

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