移植到成年脊髓中的谱系受限神经前体细胞的磁共振成像。

MR imaging of lineage-restricted neural precursors following transplantation into the adult spinal cord.

作者信息

Lepore A C, Walczak P, Rao M S, Fischer I, Bulte J W M

机构信息

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.

出版信息

Exp Neurol. 2006 Sep;201(1):49-59. doi: 10.1016/j.expneurol.2006.03.032. Epub 2006 Jun 9.

Abstract

Neural precursor cell (NPC) transplantation is a promising strategy for treatment of CNS injuries and neurodegenerative disorders because of potential for cell replacement. An important element of future clinical applications is development of a non-invasive procedure to follow NPC fate. We show that neuronal-restricted precursors (NRPs) and glial-restricted precursors (GRPs), NPCs with lineage restrictions for neurons and glia, respectively, can be labeled in vitro with the superparamagnetic iron oxide contrast agent Feridex. Following engraftment into intact adult spinal cord, labeled cells robustly survived in white and gray matter and migrated selectively along white matter tracts up to 5 mm. Localization of cells was reliably established using ex vivo magnetic resonance imaging of spinal cords. Imaging coincided with histological detection of iron and the human alkaline phosphatase transgene in most grafting sites, including the stream of migrating cells. Following transplantation, magnetically labeled cells exhibited mature morphologies and differentiated into neurons, astrocytes, and oligodendrocytes, similar to grafts of unlabeled NRPs and GRPs. Interestingly, Feridex-labeled cells, but not unlabeled cells, induced influx of ED1-positive macrophages/microglia. Small numbers of these phagocytic cells took up iron from grafted cells, while the majority of Feridex label was found in transplanted cells. We conclude that Feridex labeling does not inhibit NPC differentiation and can be used to reliably localize NPCs by MRI following engraftment into adult CNS, with the possible exception of areas of rapidly proliferating cells. The present results are relevant for MR-guided clinical application of transplantation strategies in treatment of spinal cord injury and other CNS pathologies.

摘要

神经前体细胞(NPC)移植是治疗中枢神经系统损伤和神经退行性疾病的一种很有前景的策略,因为它具有细胞替代的潜力。未来临床应用的一个重要因素是开发一种非侵入性程序来追踪NPC的命运。我们发现,神经元限制性前体细胞(NRP)和胶质细胞限制性前体细胞(GRP),即分别对神经元和胶质细胞具有谱系限制的NPC,可以在体外用超顺磁性氧化铁造影剂Feridex进行标记。将标记的细胞植入成年完整脊髓后,它们在白质和灰质中大量存活,并沿着白质束选择性迁移达5毫米。通过脊髓的离体磁共振成像可靠地确定了细胞的定位。成像结果与大多数移植部位(包括迁移细胞流)中铁和人碱性磷酸酶转基因的组织学检测结果一致。移植后,磁性标记的细胞呈现出成熟的形态,并分化为神经元、星形胶质细胞和少突胶质细胞,类似于未标记的NRP和GRP移植。有趣的是,Feridex标记的细胞而非未标记的细胞诱导了ED1阳性巨噬细胞/小胶质细胞的流入。少数这些吞噬细胞从移植细胞中摄取铁,而大部分Feridex标记物存在于移植细胞中。我们得出结论,Feridex标记不会抑制NPC的分化,并且在植入成年中枢神经系统后可通过MRI可靠地定位NPC,但快速增殖细胞区域可能除外。目前的结果与脊髓损伤和其他中枢神经系统疾病治疗中移植策略的磁共振引导临床应用相关。

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