Intrastriatal ventral mesencephalic xenografts of porcine tissue in rats: Immune responses and functional effects
Intrastriatal ventral mesencephalic xenografts of porcine tissue in rats: Immune responses and functional effects
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DOI：
10.1177/096368970000900211
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发表时间：
2000-03-01
影响因子：
3.3
通讯作者：
Widner, H
中科院分区：
文献类型：
--
作者：
Larsson, LC;Czech, KA;Widner, H
移植其他物种的神经组织有可能改善神经退行性疾病患者的功能。我们研究了胚胎猪多巴胺能神经元移植到帕金森病大鼠模型中的功能效应，以及免疫抑制和非免疫抑制宿主对移植物的免疫反应。23只单侧6-羟基多巴胺损伤的大鼠在右侧纹状体中接受了分离的27天龄的胚胎猪腹侧中脑组织。18只大鼠在整个14周期间接受环孢素（10 mg/kg，IF，每日），前4天联合泼尼松龙（20 mg/kg，IF，每日）。5只大鼠作为非免疫抑制对照。每隔3周对所有大鼠进行安非他明诱导的旋转行为测试。由于治疗的严重副作用，两只免疫抑制大鼠被排除在外。12周时，16只免疫抑制大鼠中有9只出现功能恢复。6只动物在14周时保持功能恢复，平均含有5750 +/- 1450（SEM）多巴胺能神经元。在9和14周之间，三只免疫抑制的大鼠根据旋转评分和细胞浸润的免疫组织化学显示排斥移植物。另外一只免疫抑制大鼠在14周时显示持续排斥的证据。在正在进行的或最近的排斥反应的动物的纹状体中含有大量的CD 4-和CD 8-阳性淋巴细胞，NK细胞，巨噬细胞和小胶质细胞，而瘢痕组织中发现移植物在较早的时间点（ra = 11）拒绝的大鼠。胚胎猪腹侧中脑组织在成年大鼠纹状体中成熟，重新支配宿主脑，并恢复行为缺陷。免疫抑制治疗对于移植物的长期存活和功能恢复是必要的，但不能充分防止排斥机制。猪神经组织是一个有趣的替代胚胎人组织脑内移植在神经退行性疾病。然而，为了在不一致的异种组合中实现稳定的移植物存活，需要适当的免疫抑制治疗或供体组织修饰。
Transplantation of neural tissue from other species has the potential to improve function in patients with neurodegenerative disorders. We investigated the functional effects of embryonic porcine dopaminergic neurons transplanted in a rat model of Parkinson's disease and the immune responses to the grafts in immunosuppressed and nonimmunosuppressed hosts. Twenty-three rats with unilateral 6-hydroxydopamine lesions received dissociated, 27-day-old embryonic porcine ventral mesencephalic tissue in the right striatum. Eighteen rats received cyclosporine (10 mg/kg, IF, daily) during the whole period of 14 weeks, in combination with prednisolone (20 mg/kg, IF, daily) the first 4 days. Five rats served as nonimmunosuppressed controls. All rats were tested For amphetamine-induced rotational behavior at 3-week intervals. Two immunosuppressed rats were excluded due to severe side effects of the treatment. Functional recovery was seen in 9 of 16 immunosuppressed rats at 12 weeks. Six animals remained functionally recovered at 14 weeks and contained an average of 5750 +/- 1450 (SEM) dopaminergic neurons. Between 9 and 14 weeks, three immunosuppressed rats rejected their grafts, based on rotation scores and immunohistochemical demonstration of cell infiltrates. One additional immunosuppressed rat showed evidence of ongoing rejection at 14 weeks. The striata in animals with ongoing or recent rejection contained large numbers of CD4- and CD8-positive lymphocytes, NK cells, macrophages, and microglia cells, whereas scar tissue was found in rats with grafts rejected at earlier time points (ra = 11). Embryonic porcine ventral mesencephalic tissue matures in the adult rat striatum, reinnervates the host brain, and restores behavioral defects. Immunosuppressive treatment was necessary for long-term graft survival and functional recovery, but did not sufficiently protect from rejection mechanisms. Porcine neural tissue is an interesting alternative to embryonic human tissue for intracerebral transplantation in neurodegenerative diseases. However, to achieve stable graft survival in discordant xenogeneic combinations, an appropriate immunosuppressive treatment or donor tissue modifications are needed.