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 July 1, 2011; First published June 13, 2011
Citation Information: J Clin Invest. 2011;121(7):2808-2820. https://doi.org/10.1172/JCI44489.
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Categories: Research Article Neuroscience

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

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 3

IH and ICV transplantation of human OE-MSCs improved hippocampus-dependent learning and memory.

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IH and ICV transplantation of human OE-MSCs improved hippocampus-depende...
Cognitive capacities of mice were assessed in the olfactory tubing maze (A–D) and the Morris water maze (E and F). Associative or spatial memory in mice was assessed 3 weeks after lesion (A, C, and E) and 4 weeks after cell or culture medium transplantation (B, D, and F). (A–D) Mean percentage of correct responses was obtained during 5 training sessions of 20 trials per day. (A and C) Lesioned mice (n = 2 × 16) exhibited significant impairment in an associative memory task when compared with control mice (n = 2 × 8). 4 weeks after cell implantation in the lesioned sites (B) or in the lateral ventricles (D), grafted mice (grafted, n = 2 × 8) demonstrated a significant improvement in associative memory when compared with vehicle-grafted mice (sham-grafted, n = 2 × 8). (E and F) Graphs showing the mean latencies to reach the platform during 5 training sessions of 4 trials per day. (E) Lesioned mice (n = 32) exhibited significant impairment in a visuospatial learning task when compared with control mice (n = 8). 4 weeks after cell implantation in the lesioned sites (grafted IH, n = 8) or in the lateral ventricles (grafted ICV, n = 8), grafted mice demonstrated a significant improvement in spatial learning and memory when compared with vehicle-grafted mice (sham-grafted and dead cells, n = 8, respectively). See also Supplemental Table 1 and Supplemental Videos 1 and 2. *P < 0.05; **P < 0.01; #P < 0.001.