Detection of intranasally delivered bone marrow-derived mesenchymal stromal cells in the lesioned mouse brain: a cautionary report.
Detection of intranasally delivered bone marrow-derived mesenchymal stromal cells in the lesioned mouse brain: a cautionary report.
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DOI：
10.4061/2011/586586
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发表时间：
2011
影响因子：
4.3
通讯作者：
Cohen BM
中科院分区：
文献类型：
--
作者：
Chartoff EH;Damez-Werno D;Sonntag KC;Hassinger L;Kaufmann DE;Peterson J;McPhie D;Cataldo AM;Cohen BM
骨髓间充质基质细胞(MSCs)有望用于神经病理的自体治疗。鼻腔给药是相对非侵入性的，最近有报道称可以将MSCs输送到大脑。然而，MSCs从鼻道迁移到神经病理部位并最终存活的能力还没有得到充分的研究。在本文中，我们从表达增强型绿色荧光蛋白的转基因小鼠(以下简称MSC-EGFP细胞)中获取间充质干细胞，并将其鼻腔内接种给遭受纹状体机械性损伤的野生型小鼠。使用荧光、比色和超微结构检测方法，在MSC接种后3小时到2个月内，在大脑中检测不到GFP表达的细胞。然而，在损伤对照组和MSC-EGFP处理组小鼠的嗅球和纹状体中观察到强烈类似于GFP发射的明亮的自发荧光。在对照实验中，我们直接将MSC-EGFP植入小鼠纹状体，并在植入后1天和7天检测到GFP的强势表达。这些发现表明，在我们的条件下，经鼻腔输送的MSC-EGFP不会在大脑中存活或迁移。此外，我们的观察结果强调了在使用GFP作为细胞标记物时包括适当控制的必要性。
Bone marrow-derived mesenchymal stromal cells (MSCs) hold promise for autologous treatment of neuropathologies. Intranasal delivery is relatively noninvasive and has recently been reported to result in transport of MSCs to the brain. However, the ability of MSCs to migrate from nasal passages to sites of neuropathology and ultimately survive has not been fully examined. In this paper, we harvested MSCs from transgenic mice expressing enhanced green fluorescent protein (cells hereafter referred to as MSC-EGFP) and delivered them intranasally to wild-type mice sustaining mechanical lesions in the striatum. Using fluorescent, colorimetric, and ultrastructural detection methods, GFP-expressing cells were undetectable in the brain from 3 hours to 2 months after MSC delivery. However, bright autofluorescence that strongly resembled emission from GFP was observed in the olfactory bulb and striatum of lesioned control and MSC-EGFP-treated mice. In a control experiment, we directly implanted MSC-EGFPs into the mouse striatum and detected robust GFP expression 1 and 7 days after implantation. These findings suggest that—under our conditions—intranasally delivered MSC-EGFPs do not survive or migrate in the brain. Furthermore, our observations highlight the necessity of including appropriate controls when working with GFP as a cellular marker.
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影响因子：
6.6
作者：
Danielyan, Lusine;Schaefer, Richard;Frey, William H., II
通讯作者：
Frey, William H., II
影响因子：
5.4
作者：
Lemiale, F;Kong, WP;Nabel, GJ
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影响因子：
56.9
作者：
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通讯作者：
Blau, HM
影响因子：
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作者：
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通讯作者：
Woodbury, Dale
影响因子：
5.2
作者：
Brazelton, TR;Blau, HM
通讯作者：
Blau, HM