Characterization of Ectopic Colonies That Form in Widespread Areas of the Nervous System with Neural Stem Cell Transplants into the Site of a Severe Spinal Cord Injury
Characterization of Ectopic Colonies That Form in Widespread Areas of the Nervous System with Neural Stem Cell Transplants into the Site of a Severe Spinal Cord Injury
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DOI：
10.1523/jneurosci.3066-14.2014
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发表时间：
2014-10-15
影响因子：
5.3
通讯作者：
Bonner, Joseph F.
中科院分区：
文献类型：
--
作者：
Steward, Oswald;Sharp, Kelli G.;Bonner, Joseph F.
我们以前报道过胎儿神经干细胞（NSCs）移植到脊髓横断部位后，在神经系统的广泛区域形成异位菌落。在这里，我们描述了菌落的发生率、分布和细胞组成。从表达GFP的大鼠的E14脊髓中收获的NSCs用生长因子混合物处理，并移植到完全脊髓横断的部位。移植2个月后对脊髓和脑组织进行组织学分析。在距移植物很远的脊髓中央管、脑干和脊髓表面以及第四脑室均发现异位菌落。50%的大鼠有菌落，大多数大鼠有多个菌落。轴突从殖民地延伸到宿主中枢系统。集落对巢蛋白（一种神经前体细胞的标记物）呈强烈阳性，包含突状树突的neun阳性细胞、gfap阳性星形胶质细胞、APC/ cc1阳性少突胶质细胞和ki -67阳性细胞，表明正在进行增殖。立体学分析显示，在第四脑室的一个菌落中估计有21,818个细胞，其中1005个（5%）为Ki-67阳性。对突触标记物（synaptophysin和VGluT-1）的免疫染色显示，菌落中有大量synaptophysin阳性的斑点，而VGluT-1阳性的斑点较少。在脊髓和脑的狭窄空间内，nsc来源的细胞团持续扩大可产生可归因于附近组织受压的症状。其他具有自我更新能力的细胞类型是否也能形成菌落还有待确定。
We reported previously the formation of ectopic colonies in widespread areas of the nervous system after transplantation of fetal neural stem cells (NSCs) into spinal cord transection sites. Here, we characterize the incidence, distribution, and cellular composition of the colonies. NSCs harvested from E14 spinal cords from rats that express GFP were treated with a growth factor cocktail and grafted into the site of a complete spinal cord transection. Two months after transplant, spinal cord and brain tissue were analyzed histologically. Ectopic colonies were found at long distances from the transplant in the central canal of the spinal cord, the surface of the brainstem and spinal cord, and in the fourth ventricle. Colonies were present in 50% of the rats, and most rats had multiple colonies. Axons extended from the colonies into the host CNS. Colonies were strongly positive for nestin, a marker for neural precursors, and contained NeuN-positive cells with processes resembling dendrites, GFAP-positive astrocytes, APC/CC1-positive oligodendrocytes, and Ki-67-positive cells, indicating ongoing proliferation. Stereological analyses revealed an estimated 21,818 cells in a colony in the fourth ventricle, of which 1005 (5%) were Ki-67 positive. Immunostaining for synaptic markers (synaptophysin and VGluT-1) revealed large numbers of synaptophysin-positive puncta within the colonies but fewer VGluT-1 puncta. Continuing expansion of NSC-derived cell masses in confined spaces in the spinal cord and brain could produce symptoms attributable to compression of nearby tissue. It remains to be determined whether other cell types with self-renewing potential can also form colonies.