Long-term fate of neural precursor cells following transplantation into developing and adult CNS
Long-term fate of neural precursor cells following transplantation into developing and adult CNS
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DOI：
10.1016/j.neuroscience.2005.12.043
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Fischer, I
中科院分区：
文献类型：
--
作者：
Lepore, AC;Neuhuber, B;Fischer, I
移植神经前体细胞以替代丢失或功能障碍的CNS细胞的成功策略需要移植细胞的长期存活并与宿主系统整合，可能持续受体的生命。同样重要的是要证明移植不会导致不良后果。很少有研究检查移植的神经前体细胞在中枢神经系统中的长期特性，特别是在成人的非神经源性区域。本研究的目的是广泛表征移植到发育和成人CNS（脑和脊髓）长达15个月后，包括移植物衍生的神经元与宿主的整合的神经前体细胞的定义群体的命运。具体而言，我们采用了神经元限制性前体和胶质限制性前体，它们分别代表神经元和胶质细胞命运的谱系限制的神经前体细胞。从表达标记基因人胎盘碱性磷酸酶的转基因供体大鼠的胚胎13.5天胎儿脊髓制备移植细胞，以实现稳定和可靠的移植物追踪。我们发现，在发育和成年CNS移植细胞表现出长期存活，形态成熟，广泛的分布和分化成所有成熟的CNS细胞类型（神经元，星形胶质细胞和少突胶质细胞）。移植物衍生的神经元也形成突触，如通过电子显微镜鉴定的，表明移植的神经前体细胞与成人CNS整合。此外，移植物未导致任何明显的有害结果。我们没有检测到肿瘤形成，细胞没有定位到不需要的位置，移植部位也没有明显的免疫反应。神经元限制性前体细胞和胶质细胞限制性前体细胞的长期稳定性和无不良反应表明，谱系限制性神经前体细胞移植可作为CNS损伤和变性的有效和安全的替代疗法。(C)2006由Elsevier Ltd代表IBRO出版。
Successful strategies for transplantation of neural precursor cells for replacement of lost or dysfunctional CNS cells require long-term survival of grafted cells and integration with the host system, potentially for the life of the recipient. It is also important to demonstrate that transplants do not result in adverse outcomes. Few studies have examined the long-term properties of transplanted neural precursor cells in the CNS, particularly in non-neurogenic regions of the adult. The aim of the present study was to extensively characterize the fate of defined populations of neural precursor cells following transplantation into the developing and adult CNS (brain and spinal cord) for up to 15 months, including integration of graft-derived neurons with the host. Specifically, we employed neuronal-restricted precursors and glial-restricted precursors, which represent neural precursor cells with lineage restrictions for neuronal and glial fate, respectively. Transplanted cells were prepared from embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the marker gene human placental alkaline phosphatase to achieve stable and reliable graft tracking. We found that in both developing and adult CNS grafted cells showed long-term survival, morphological maturation, extensive distribution and differentiation into all mature CNS cell types (neurons, astrocytes and oligodendrocytes). Graft-derived neurons also formed synapses, as identified by electron microscopy, suggesting that transplanted neural precursor cells integrated with adult CNS. Furthermore, grafts did not result in any apparent deleterious outcomes. We did not detect tumor formation, cells did not localize to unwanted locations and no pronounced immune response was present at the graft sites. The long-term stability of neuronal-restricted precursors and glial-restricted precursors and the lack of adverse effects suggest that transplantation of lineage-restricted neural precursor cells can serve as an effective and safe replacement therapy for CNS injury and degeneration. (C) 2006 Published by Elsevier Ltd on behalf of IBRO.