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Engraftment of human nasal olfactory stem cells restores neuroplasticity in mice with hippocampal lesions
Emmanuel Nivet, … , François Féron, François S. Roman
Emmanuel Nivet, … , François Féron, François S. Roman
Published June 13, 2011
Citation Information: J Clin Invest. 2011;121(7):2808-2820. https://doi.org/10.1172/JCI44489.
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Research Article Neuroscience

Engraftment of human nasal olfactory stem cells restores neuroplasticity in mice with hippocampal lesions

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Abstract

Stem cell–based therapy has been proposed as a potential means of treatment for a variety of brain disorders. Because ethical and technical issues have so far limited the clinical translation of research using embryonic/fetal cells and neural tissue, respectively, the search for alternative sources of therapeutic stem cells remains ongoing. Here, we report that upon transplantation into mice with chemically induced hippocampal lesions, human olfactory ecto–mesenchymal stem cells (OE-MSCs) — adult stem cells from human nasal olfactory lamina propria — migrated toward the sites of neural damage, where they differentiated into neurons. Additionally, transplanted OE-MSCs stimulated endogenous neurogenesis, restored synaptic transmission, and enhanced long-term potentiation. Mice that received transplanted OE-MSCs exhibited restoration of learning and memory on behavioral tests compared with lesioned, nontransplanted control mice. Similar results were obtained when OE-MSCs were injected into the cerebrospinal fluid. These data show that OE-MSCs can induce neurogenesis and contribute to restoration of hippocampal neuronal networks via trophic actions. They provide evidence that human olfactory tissue is a conceivable source of nervous system replacement cells. This stem cell subtype may be useful for a broad range of stem cell–related studies.

Authors

Emmanuel Nivet, Michel Vignes, Stéphane D. Girard, Caroline Pierrisnard, Nathalie Baril, Arnaud Devèze, Jacques Magnan, Fabien Lanté, Michel Khrestchatisky, François Féron, François S. Roman

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Figure 6

Human OE-MSCs stimulated endogenous neurogenesis after transplantation in lesioned hippocampi.

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Human OE-MSCs stimulated endogenous neurogenesis after transplantation i...
5 weeks after grafting, brain sections of mice injected with BrdU twice a day during 3 days following cell implantation (n = 5 for each group) were immunostained with anti-NeuN (green) and anti-BrdU antibodies (red) (A–D). Quantification of BrdU+/NeuN+ cells in DG indicated an increased number of mitotic cells in grafted (IH) mice when compared with sham-grafted (IH) (P < 0.05) and control (P < 0.01) mice (E). DCX immunohistochemistry revealed the presence of immature neurons in the DG of control (G) and grafted (IH) (F, H) mice. As shown in (H), no GFP+ human OE-MSC was found to express DCX. Lesioned mice with IH transplant of human OE-MSCs (grafted [IH], n = 5) exhibited a higher percentage of DCX-positive cells when compared with vehicle-treated (sham-grafted [IH], n = 5) and control (n = 5) mice (I). (E and I). Scale bars: 10 μm (A–C); 100 μm (D, F, G, and H). *P < 0.05; **P < 0.01.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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