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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 7

Human OE-MSCs transplanted into the cerebrospinal fluid (CSF) of hippocampus-lesioned mice survived at least 5 weeks, migrated, and differentiated into neurons.

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Human OE-MSCs transplanted into the cerebrospinal fluid (CSF) of hippoca...
(A) Increased density of GFP+ cells within the pyramidal cell body layers demonstrated the ability of human OE-MSCs to migrate from the CSF toward the injury zone. (B) As demonstrated by confocal image reconstitution using projection transparency (see also Supplemental Video 4), exogenous GFP+ cells were also remarkably distributed within the granule cell body layers of the DG. The insert indicates that not a single human OE-MSC expressed the astrocytic marker GFAP (red). (C and D) Within the CA3 field, some pyramidal cell–like and interneuron-like GFP+ human OE-MSCs (green) expressed III–β-tubulin (red) (white arrows in C, yellow arrow in D), but others were immunonegative for this immature neuronal marker (green arrows in D). (E) Exogenous GFP+ cells migrated as well in other cerebral areas (cortical area in E), but remained immunonegative for the mature neuronal marker MAP2 (red). (F) GFP+ cells exhibiting an undifferentiated morphology were found at the margin of the ventricular areas. Scale bars: 100 μm (A, C, D, E, and F); 30 μm (B, insert). See also Supplemental Video 4.
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