Transplantation of Embryonic and Adult Neural Stem Cells in the Granuloprival Cerebellum of the Weaver Mutant Mouse
Transplantation of Embryonic and Adult Neural Stem Cells in the Granuloprival Cerebellum of the Weaver Mutant Mouse
复制标题
DOI：
10.1002/stem.83
复制
发表时间：
2009-01-01
期刊：
影响因子：
5.2
通讯作者：
Steindler, Dennis A.
中科院分区：
文献类型：
--
作者：
Chen, K. Amy;Lanuto, Derek;Steindler, Dennis A.
许多研究探索了不同干细胞和祖细胞在各种神经退行性疾病模型中替代高危神经元群的潜力。这项研究提供了将两种不同的干细胞/祖细胞群移植到织布神经突变小鼠出生后小脑内的并行方法的数据，即小脑源性多能星形胶质细胞干细胞和胚胎干细胞源性神经前体细胞，以进行比较分析。我们在这里表明，两个供体群体都能在颗粒私有宿主环境中存活、迁移并似乎开始分化为神经元。这些不同的干细胞/祖细胞群都没有采用显着的区域特异性特征，尽管早期的研究表明这些细胞在置于许可/指导性环境中时有可能对体内线索做出反应。然而，这里提供的数据表明，编织者纯合或杂合大脑中存在的分子和细胞缺陷可能会促进供体细胞对神经元表型获得的反应稍微更积极。因此，在适合细胞替换的受损宿主环境和退化的细胞环境之间可能存在着良好的平衡，在退化的细胞环境中，它可能太有害而无法支持广泛的神经元分化和功能性细胞整合。这些发现与越来越多的研究一起表明，成功的细胞替代在很大程度上取决于供体细胞的潜力与受体环境的特定病理条件之间的相互作用，并且涉及使用神经干细胞的神经系统疾病的紧急疗法仍然需要完善。干细胞2009； 27：1625-1634
Numerous studies have explored the potential of different stem and progenitor cells to replace at-risk neuronal populations in a variety of neurodegenerative disease models. This study presents data from a side-by-side approach of engrafting two different stem/progenitor cell populations within the postnatal cerebellum of the weaver neurological mutant mouse-cerebellar-derived multipotent astrocytic stem cells and embryonic stem cell-derived neural precursors-for comparative analysis. We show here that both donor populations survive, migrate, and appear to initiate differentiation into neurons within the granuloprival host environment. Neither of these disparate stem/progenitor cell populations adopted significant region-specific identities, despite earlier studies that suggested the potential of these cells to respond to in vivo cues when placed in a permissive/instructive milieu. However, data presented here suggest that molecular and cellular deficits present within weaver homozygous or heterozygous brains may promote a slightly more positive donor cell response toward acquisition of a neuronal phenotype. Hence, it is likely that a fine balance exists between a compromised host environment that is amenable to cell replacement and that of a degenerating cellular milieu where it is perhaps too deleterious to support extensive neuronal differentiation and functional cellular integration. These findings join a growing list of studies that show successful cell replacement depends largely on the interplay between the potentiality of the donor cells and the specific pathological conditions of the recipient environment, and that emergent therapies for neurological disorders involving the use of neural stem cells still require refinement. STEM CELLS 2009; 27: 1625-1634