Sustained survival of xenografted human neural stem/progenitor cells in experimental brain trauma despite discontinuation of immunosuppression
Sustained survival of xenografted human neural stem/progenitor cells in experimental brain trauma despite discontinuation of immunosuppression
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DOI：
10.1016/j.expneurol.2005.12.035
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发表时间：
2006-06-01
影响因子：
5.3
通讯作者：
Mathiesen, Tiit
中科院分区：
文献类型：
--
作者：
Wennersten, Andre;Holmin, Staffan;Mathiesen, Tiit
神经干细胞已成为一种有前途的治疗中枢神经系统疾病和损伤的工具。在临床环境中，培养的人类神经干/祖细胞（hNSC）是移植到受损大脑的一个有吸引力的可能性。然而，hNSC移植需要毒性免疫抑制治疗以避免排斥反应。本研究的目的是评估环孢素A缩短免疫抑制时间是否会影响hNSC移植到大鼠局灶性脑损伤部位后的存活和分化。hNSC异种移植到海马体和实验诱导的皮质挫伤的内侧边界。免疫抑制期为6周、3周或无免疫抑制。用免疫组织化学方法分析移植的人细胞状态。在移植后6周，两个免疫抑制组在移植物存活、迁移或增殖方面无统计学差异。相比之下，非免疫抑制组的移植物存活率极低。此外，移植细胞中分化标志物巢蛋白（nestin）、神经元核（NeuN）和胶质原纤维酸性蛋白（GFAP）的表达在免疫抑制组和免疫抑制组之间无显著差异。第四组8只免疫抑制3周的动物存活6个月。其中5只大鼠在海马体中表现出强劲的移植物存活，在皮层中表现出分散的细胞。本研究证明了免疫抑制的重要性，同时也证明了在不影响移植物hNSC表型的情况下缩短免疫抑制的可能性。(c) 2006爱思唯尔公司版权所有。
Neural stein cells have emerged as a promising therapeutic tool in CNS disease and injuries. In the clinical setting, cultured human neural stem/progenitor cells (hNSC) are an attractive possibility for transplantation to the damaged brain. However, transplantation of hNSC requires toxic immunosuppressive treatment to avoid rejection. The aim of the current study was to evaluate if shortening the duration of immuno suppression by cyclosporin A would affect hNSC survival and differentiation after transplantation to the site of a focal brain injury in the rat. hNSC were xenografted to the hippocampus and the medial limit of an experimentally induced cortical contusion. The animals received immumosuppression for either 6 or 3 weeks or no immunosuppression. The status of the grafted human cells was analysed by immunohistochemistry. No statistically significant differences were observed between the two immunosuppressed groups regarding graft survival, migration or proliferation at 6 weeks post-transplantation. In contrast, the graft survival was extremely poor in the non-immunosuppressed group. Furthermore, the expression of the differentiation markers nestin, neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) in the transplanted cells did not differ significantly between the two immunosuppressed groups. Moreover, a fourth group of eight animals that were immunosuppressed for 3 weeks were allowed to survive for 6 months. Five of these rats demonstrated robust graft survival in the hippocampus and scattered cells in the cortex. This study demonstrates the importance of immunosuppression but also the possibility of shortening immunosuppression without impacting on the phenotype of the grafted hNSC. (c) 2006 Elsevier Inc. All rights reserved.