The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features
The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features
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DOI：
10.1093/brain/awv089
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发表时间：
2015-06-01
期刊：
影响因子：
14.5
通讯作者：
Molina-Holgado, Eduardo
中科院分区：
文献类型：
--
作者：
Garcia-Ovejero, Daniel;Arevalo-Martin, Angel;Molina-Holgado, Eduardo
一些实验室已经描述了啮齿动物脊髓室管膜中存在未分化的前体细胞，其作用可能类似于干细胞。然而，有报告显示，人类在生命的第二个十年后，该区域被封闭和分解，尽管这在很大程度上被忽视或解释为死后的人工制品。为了深入了解成人脊髓室管膜区域的通畅情况、实际结构和分子特性，我们采用了三种方法：（i）通过 MRI，我们评估了 59 名对照受试者、99 名创伤性脊髓损伤患者和 26 名非创伤性脊髓损伤患者的中央管通畅情况。我们观察到，无论性别如何，绝大多数 18 岁以上的人在整个脊髓长度上都没有中央管，无论是在健康对照组还是在受伤后； (ii) 通过组织学和免疫组织化学，我们描述了未病变室管膜区域的形态学特性，该区域显示血管周围假玫瑰花结的存在，这是室管膜瘤的一个共同特征； (iii) 通过激光捕获显微切割，然后使用 TaqMan (R) 低密度阵列，我们研究了室管膜区域的基因表达谱，发现它主要富含与低度或静止室管膜瘤相容的基因（53 个基因）；该区域仅富含 14 个与神经源性生态位相关的基因。总之，我们在此证明，成人脊髓中主要不存在中央管，而是被形态和分子上与啮齿动物和其他灵长类动物所描述的结构不同的结构所取代。所提供的数据表明室管膜区域更有可能让人想起低度室管膜瘤。因此，基于动物模型将该区域的最终治疗潜力直接转化为成人患者应谨慎对待。
Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan (R) low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution.