Labandeira-Garcia J L, Wictorin K, Cunningham E T, Björklund A
Department of Medical Cell Research, University of Lund, Sweden.
Neuroscience. 1991;42(2):407-26. doi: 10.1016/0306-4522(91)90385-2.
The morphological maturation of cell suspension grafts of fetal striatal tissue (obtained from 14-15-day-old rat fetuses) was followed from two days to eight weeks after implantation into intact and ibotenic acid-lesioned striata of adult rats. The development of host afferent innervation of the grafts from the substantia nigra (tyrosine hydroxylase immunoreactive), mesencephalic raphe (serotonin immunoreactive), and the frontal cortex (anterogradely labelled with Phaseolus vulgaris leucoagglutinin) were revealed by immunohistochemistry. During the first weeks post-grafting, the striatal implants consisted of a mixture of mature- and immature-looking cell clusters. Grafts implanted into ibotenic acid-lesioned striatum grew rapidly (about five-fold) in volume over the first week. The areas of immature (probably proliferating) cells gradually disappeared, and by six to eight weeks the grafts had a fully mature appearance with patches of neurons which stained densely for DARPP-32 (i.e. were striatum-like) embedded within areas of essentially DARPP-32-negative (i.e. non-striatum-like) tissue. Peripheral clusters of grafted cells gradually intermingled with nearby areas of the surrounding lesioned host, and already by two to four days after implantation, coarse and densely immunoreactive host fibres from the substantia nigra, mesencephalic raphe and frontal cortex were present within the grafts. By four to five days the first DARPP-32-immunoreactive neurons appeared in patches within the mature portions of the grafts, and one to two days later the tyrosine hydroxylase-positive fibres began to sprout thin axons selectively within the DARPP-32-positive patches. Similarly, the serotonergic and cortical fibres in the grafts increased in number over the next two weeks, but they showed no preference for the DARPP-32-positive regions. Rich terminal networks were established by two to three weeks post-grafting, and by six to eight weeks the nigral, raphe and cortical afferents had reached terminal densities similar to those seen previously in long-term surviving grafts. Grafts implanted into dopamine-denervated hosts showed a normal morphological maturation of both DARPP-32-positive and -negative areas, although no tyrosine hydroxylase-positive innervation appeared within the grafts. Grafts implanted into non-lesioned striata did not grow beyond their initial size. The implanted cells showed less intermingling with the surrounding host striatum, thus resulting in sharply delineated graft-host borders. DARPP-32-positive patches developed, but they were smaller in size and generally present only in the most peripheral graft portions.(ABSTRACT TRUNCATED AT 400 WORDS)
将取自14至15日龄大鼠胎儿的胎儿纹状体组织的细胞悬液移植物植入成年大鼠完整和鹅膏蕈氨酸损伤的纹状体中，观察其从植入后两天到八周的形态成熟过程。通过免疫组织化学揭示了来自黑质（酪氨酸羟化酶免疫反应阳性）、中脑缝际核（5-羟色胺免疫反应阳性）和额叶皮质（用菜豆白细胞凝集素进行顺行标记）的移植物宿主传入神经支配的发育情况。在移植后的最初几周，纹状体植入物由外观成熟和不成熟的细胞簇混合组成。植入鹅膏蕈氨酸损伤纹状体的移植物在第一周内体积迅速增大（约五倍）。不成熟（可能在增殖）细胞的区域逐渐消失，到六至八周时，移植物呈现出完全成熟的外观，有一些DARPP-32染色浓密的神经元斑块（即类似纹状体）嵌入基本为DARPP-32阴性（即非纹状体样）的组织区域内。移植细胞的周边簇逐渐与周围损伤宿主的附近区域混合，在植入后两到四天，来自黑质、中脑缝际核和额叶皮质的粗大且免疫反应强烈的宿主纤维就已出现在移植物内。到四至五天时，第一批DARPP-32免疫反应阳性神经元出现在移植物成熟部分的斑块中，一到两天后，酪氨酸羟化酶阳性纤维开始在DARPP-32阳性斑块内选择性地长出细轴突。同样，移植物中的5-羟色胺能纤维和皮质纤维在接下来的两周内数量增加，但它们对DARPP-32阳性区域没有偏好。移植后两到三周建立了丰富的终末网络，到六至八周时，黑质、缝际核和皮质的传入神经终末密度已达到与先前长期存活移植物中所见相似的水平。植入多巴胺去神经支配宿主的移植物中，DARPP-32阳性和阴性区域均表现出正常的形态成熟，尽管移植物内未出现酪氨酸羟化酶阳性神经支配。植入未损伤纹状体的移植物大小没有超过其初始大小。植入的细胞与周围宿主纹状体的混合较少，因此导致移植物与宿主的边界清晰。DARPP-32阳性斑块形成，但它们尺寸较小，通常仅出现在移植物最外围部分。（摘要截断于400字）
