Integration of transplanted cultured Schwann cells into the long myelinated fiber tracts of the adult spinal cord
Integration of transplanted cultured Schwann cells into the long myelinated fiber tracts of the adult spinal cord
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DOI：
10.1006/exnr.1997.6502
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发表时间：
1997-06-01
影响因子：
5.3
通讯作者：
Raisman, G
中科院分区：
文献类型：
--
作者：
Li, Y;Raisman, G
将从新生大鼠坐骨神经培养的约10,000个纯化施万细胞的悬浮液移植到成年大鼠一侧皮质脊髓束上颈水平的离散部位。移植后 4 天起，p75（低亲和力神经营养蛋白受体）免疫染色显示，移植物由雪旺细胞的中央团块和沿着弯曲血管的血管周围空间的细长雪旺细胞袖口组成（其中大部分是在移植反应中形成的）。离开中央质量和血管周围袖口的雪旺细胞沿着宿主皮质脊髓束的头尾轴以严格的线性方向迁移。根据它们迁移的区域，移植的雪旺细胞采用两种截然不同的形式：（1）行雪旺细胞，在宿主少突胶质细胞和星形细胞细胞体的行内单独或成群地迁移，是无过程的，而是立方形的砖状细胞（大小约为8 x 12μm）。 (2)相比之下，束间雪旺细胞单独迁移或以绳状小群交织在一起，散布在宿主皮质脊髓束的轴突中，是较大的、对称的双极细胞，其突起约100-120μm长、2μm宽，具有凸出的卵圆形核，位于中央放置的约10μm宽的细胞体中。大约 6 周后，束间雪旺细胞的 p75 免疫反应性下调。然而，早在移植后 10 天，外周髓鞘蛋白、P-0、半薄切片和电子显微镜的免疫染色表明，这些雪旺细胞并未丢失，但它们在移植区域的宿主皮质脊髓轴突节段上有髓鞘化。相反，雪旺细胞行不表达 P-0 或形成髓磷脂。它们在长期存活后保留了 p75 免疫反应性（大概是因为它们无法接触束轴突）。行雪旺细胞也比束间雪旺细胞迁移得更远（可能是其维持的 p75 表达的函数），从原始移植位点开始单独分散至少 8 毫米。我们之前对皮质脊髓束病变的研究表明，肥大的星形胶质细胞过程形成了“闭合”疤痕，该疤痕隔离了中央无星形胶质细胞的区域，并完全破坏了皮质脊髓束过程的正常纵向排列。相比之下，虽然目前的施万细胞移植在同一时间过程中诱导了相当的星形胶质细胞肥大，但星形胶质细胞过程仍然能够穿透没有被围住的移植部位，因此宿主皮质脊髓束星形胶质细胞骨架的纵向排列在整个移植区域中保持完整。这些观察结果表明施万细胞可以紧密整合到有髓鞘成体宿主皮质脊髓束的细胞结构中。这种整合并不是受损区域的随机分散：它涉及与宿主道中存在的细胞元件的直接相互作用，它尊重宿主道神经胶质细胞的复杂和规则的组织，并导致形成精确排列的中央和外周组织镶嵌体。 (C) 1997 年学术出版社。
A suspension of about 10,000 purified Schwann cells cultured from the neonatal rat sciatic nerve was transplanted into a discrete site in the upper cervical level of the corticospinal tract of one side in adult rats. From 4 days after transplantation immunostaining for p75 (low-affinity neurotrophin receptor) showed that the transplants consisted of a central mass of Schwann cells and cuffs of elongated Schwann cells along the perivascular space of curving blood vessels (most of which had been formed in response to the transplantation). Schwann cells leaving the central mass and perivascular cuffs migrated in strictly linear orientation along the rostrocaudal axis of the host corticospinal tract. According to the territory through which they migrated, the transplanted Schwann cells adopted two quite different forms: (1) The row Schwann cells, which migrated singly or in groups within the rows of host oligodendrocytic and astrocytic cell bodies, were non-process-bearing, rather cuboidal, brick-like cells (about 8 x 12 mu m in size). (2) In contrast, the interfascicular Schwann cells, which migrated singly or intertwined in rope-like small groups interspersed among the axons of the host corticospinal tract, were larger, symmetrically bipolar cells, with processes about 100-120 mu m long and 2 pm wide and bulging, ovoid nuclei, located in centrally placed cell bodies about 10 mu m across. After about 6 weeks, the p75 immunoreactivity of the interfascicular Schwann cells had become downregulated. However, from as early as 10 days after transplantation, immunostaining for the peripheral myelin protein, P-0, semithin sections, and electron microscopy showed that these Schwann cells were not lost, but that they had myelinated the segments of the host corticospinal axons in the region of the transplant. In contrast, the row Schwann cells did not express P-0 or form myelin. They retained their p75 immunoreactivity at long survivals (presumably because they were secluded from contacting the tract axons). The row Schwann cells also migrated farther than the interfascicular Schwann cells (possibly a function of their maintained p75 expression), becoming dispersed singly for at least 8 mm from the original transplant site. Our previous study of corticospinal tract lesions had shown the formation of a ''closed'' scar formed by hypertrophic astrocytic processes, which walled off a central astrocyte-free region and totally disrupted the normal longitudinal alignment of the tract astrocytic processes. In contrast, while the present Schwann cell transplants induced a comparable astrocytic hypertrophy over the same time course, the astrocytic processes remained able to penetrate the transplant site, which was not walled off, so that the longitudinal arrangement of the host corticospinal tract astrocytic skeleton was preserved intact across the region of the transplant. These observations show that Schwann cells can be intimately integrated into the cytoarchitecture of the myelinated adult host corticospinal tract. This integration is not a random dispersal in damaged areas: it involves direct interaction with the cell elements present in the host tract, it respects the complex and regular organization of the host tract glial cells, and it results in the formation of a precisely arranged mosaic of central and peripheral tissue. (C) 1997 Academic Press.