移植的胎儿神经细胞在成年海马体经海藻酸损伤的CA3区域中的存活取决于细胞特异性。

Survival of grafted fetal neural cells in kainic acid lesioned CA3 region of adult hippocampus depends upon cell specificity.

作者信息

Zaman V, Turner D A, Shetty A K

机构信息

Department of Surgery, Duke University Medical Center, Durham, North Carolina, 27710, USA.

出版信息

Exp Neurol. 2000 Feb;161(2):535-61. doi: 10.1006/exnr.1999.7304.

DOI:10.1006/exnr.1999.7304

PMID:10686075

Abstract

We hypothesize that the degree of graft cell survival within the damaged CNS correlates with the specificity of donor cells to the region of grafting. We investigated graft cell survival following transplantation of fetal micrografts into the CA3 region of the adult rat hippocampus at a time-point of 4 days after an intracerebroventricular administration of kainic acid (KA). Grafts consisted of 5'-bromodeoxyuridine (BrdU) labeled embryonic day (E) 19 cells from hippocampal fields CA3 and CA1 and E15 and E19 cells from the striatum. Absolute cell survival in these grafts was quantitatively analyzed at 1 month postgrafting, using BrdU immunostaining of serial sections and three-dimensional reconstruction of grafts. Absolute graft cell survival in lesioned CA3 was dramatically greater for cells having hippocampal origin (CA3 cells, 69% cell survival; CA1 cells, 42% cell survival) than those having nonhippocampal origin, such as striatal cells (E15 cells, 12% cell survival; E19 cells, 4% cell survival). This difference is in sharp contrast to survival of these cells in culture, where E19 cells from both hippocampal and nonhippocampal origins exhibited similar survival. Comparison of survival among hippocampal cell types indicated significantly greater survival for cells that are specific to the lesioned area (i.e., CA3 cells) than for those that are nonspecific to the lesioned area (i.e., CA1 cells). Graft cell survival in the intact CA3 region (contralateral to KA administration), however, did not differ either between cells having hippocampal and nonhippocampal origins or between CA3 and CA1 cells (CA3 cells, 26% cell survival; CA1 cells, 33% cell survival; and E15 striatal cells, 20% cell survival). These results underscore the finding that enhanced survival of fetal cell grafts in the lesioned CNS is critically dependent upon the specificity of donor fetal cells to the region of transplantation. Thus, grafting of cells that are specific to the lesioned area is a prerequisite for achieving maximal graft cell survival and integration in the lesioned host CNS.

摘要

我们推测，受损中枢神经系统内移植细胞的存活程度与供体细胞对移植区域的特异性相关。我们研究了在脑室内注射 kainic 酸（KA）4 天后，将胎儿微移植物移植到成年大鼠海马体 CA3 区域后的移植细胞存活情况。移植物由来自海马体 CA3 和 CA1 区域的 5'-溴脱氧尿苷（BrdU）标记的胚胎第 19 天（E19）细胞以及来自纹状体的 E15 和 E19 细胞组成。在移植后 1 个月，使用连续切片的 BrdU 免疫染色和移植物的三维重建对这些移植物中的绝对细胞存活情况进行了定量分析。与非海马体来源的细胞（如纹状体细胞，E15 细胞，细胞存活率为 12%；E19 细胞，细胞存活率为 4%）相比，海马体来源的细胞（CA3 细胞，细胞存活率为 69%；CA1 细胞，细胞存活率为 42%）在受损 CA3 中的绝对移植细胞存活率显著更高。这种差异与这些细胞在培养中的存活情况形成鲜明对比，在培养中，来自海马体和非海马体来源的 E19 细胞表现出相似的存活率。海马体细胞类型之间的存活比较表明，与受损区域非特异性的细胞（即 CA1 细胞）相比，受损区域特异性的细胞（即 CA3 细胞）存活率显著更高。然而，在完整的 CA3 区域（与 KA 注射对侧），海马体和非海马体来源的细胞之间以及 CA3 和 CA1 细胞之间的移植细胞存活率没有差异（CA3 细胞，细胞存活率为 26%；CA1 细胞，细胞存活率为 33%；E15 纹状体细胞，细胞存活率为 20%）。这些结果强调了一个发现，即胎儿细胞移植物在受损中枢神经系统中存活率的提高关键取决于供体胎儿细胞对移植区域的特异性。因此，移植受损区域特异性的细胞是在受损宿主中枢神经系统中实现最大移植细胞存活和整合的先决条件。