Department of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
Stem Cells Int. 2011;2011:586586. doi: 10.4061/2011/586586. Epub 2011 Nov 15.
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.
骨髓间充质基质细胞（MSCs）有望用于治疗神经病理学的自体治疗。鼻内给药相对无创，最近有报道称，它可将 MSCs 输送到大脑。然而，MSCs 从鼻腔迁移到神经病理学部位并最终存活的能力尚未得到充分检查。在本文中，我们从表达增强型绿色荧光蛋白（以下简称 MSC-EGFP）的转基因小鼠中收获 MSCs，并将其经鼻内递送至持续在纹状体中发生机械损伤的野生型小鼠。使用荧光、比色和超微结构检测方法，在 MSC 递送后 3 小时至 2 个月，在大脑中均无法检测到 GFP 表达的细胞。然而，在损伤对照和 MSC-EGFP 处理的小鼠的嗅球和纹状体中观察到强烈类似于 GFP 发射的明亮自发荧光。在对照实验中，我们直接将 MSC-EGFPs 植入小鼠纹状体，并在植入后 1 天和 7 天检测到强烈的 GFP 表达。这些发现表明——在我们的条件下——经鼻内递送的 MSC-EGFPs 在大脑中不能存活或迁移。此外，我们的观察结果强调了在使用 GFP 作为细胞标记物时，包含适当对照的必要性。
