Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary Report
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 sit...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.4061/2011/586586 |
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| author | Elena H. Chartoff Diane Damez-Werno Kai C. Sonntag Linda Hassinger Daniel E. Kaufmann Jesse Peterson Donna McPhie Anne M. Cataldo Bruce M. Cohen |
| author_facet | Elena H. Chartoff Diane Damez-Werno Kai C. Sonntag Linda Hassinger Daniel E. Kaufmann Jesse Peterson Donna McPhie Anne M. Cataldo Bruce M. Cohen |
| author_sort | Elena H. Chartoff |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b26c614f7799435a9d26af253306cefe |
| institution | OA Journals |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-b26c614f7799435a9d26af253306cefe2025-08-20T02:23:19ZengWileyStem Cells International1687-966X1687-96782011-01-01201110.4061/2011/586586586586Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary ReportElena H. Chartoff0Diane Damez-Werno1Kai C. Sonntag2Linda Hassinger3Daniel E. Kaufmann4Jesse Peterson5Donna McPhie6Anne M. Cataldo7Bruce M. Cohen8Department of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USADepartment of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USADepartment of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USADepartment of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USARagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Charlestown, MA 02129, USADepartment of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USADepartment of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USADepartment of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USADepartment of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USABone 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.http://dx.doi.org/10.4061/2011/586586 |
| spellingShingle | Elena H. Chartoff Diane Damez-Werno Kai C. Sonntag Linda Hassinger Daniel E. Kaufmann Jesse Peterson Donna McPhie Anne M. Cataldo Bruce M. Cohen Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary Report Stem Cells International |
| title | Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary Report |
| title_full | Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary Report |
| title_fullStr | Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary Report |
| title_full_unstemmed | Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary Report |
| title_short | Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary Report |
| title_sort | detection of intranasally delivered bone marrow derived mesenchymal stromal cells in the lesioned mouse brain a cautionary report |
| url | http://dx.doi.org/10.4061/2011/586586 |
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