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Articles by Emmanuel Nivet in JoVE
JoVE Neuroscience
عزل الخلايا الجذعية الأنف الشم من القوارض أو البشر
1NICN, Aix Marseille University, 2LNPM, Aix Marseille University, 3ENT Department, Aix Marseille University, 4Gene expression Laboratory, The Salk Institute for Biological Studies, 5Laboratory of Speech and Language, Aix Marseille University, 6Centre d'Investigations Cliniques en Biothérapie, Aix Marseille University
نحن هنا تصف طريقة لbiopsying المخاطية الشمية من الفئران والجيوب الأنفية الإنسان. ويمكن استخدام هذه الخزعات إما لتحديد الحالات الشاذة الجزيئية في الدماغ أو أمراض multipotent عزل الخلايا الجذعية التي يمكن استخدامها لزرع الخلايا في النماذج الحيوانية من الصدمة الدماغ / المرض.
Other articles by Emmanuel Nivet on PubMed
Perseveration Related to Frontal Lesion in Mice Using the Olfactory H-maze
The delayed reaction paradigm, consisting to discover two different rules consecutively (delayed alternation and non-alternation task) followed by a delayed reversal task, is a specific marker for the functioning of primate prefrontal cortex. Although several works in rodents report the use of operant delayed alternation tasks, in none of the studies mice with lesion of the prefrontal cortex were used in this paradigm. In the current study, mouse experiments were conducted using a new, totally automated device, the olfactory H-maze. Here, we show that unilateral lesion of the dorsomedial prefrontal cortex in mice induced similar deficits to those observed after frontal lesions in monkeys and humans. These pronounced learning deficits seem to come from difficulty elaborating a new rule and the inability to inhibit the previous rule, characterized by perseveration after prefrontal cortex lesion. The present results demonstrate that this very simple experimental paradigm using the olfactory H-maze presents the advantage to be fast (one training session) and well suited to assess the frontal functions in mice. It should be useful for testing pharmacological or stem cell approaches in order to reduce organic damages or gain insight into the cognitive functions of the frontal cortex using transgenic or gene-targeting mice.
The Human Nose Harbors a Niche of Olfactory Ectomesenchymal Stem Cells Displaying Neurogenic and Osteogenic Properties
We previously identified multipotent stem cells within the lamina propria of the human olfactory mucosa, located in the nasal cavity. We also demonstrated that this cell type differentiates into neural cells and improves locomotor behavior after transplantation in a rat model of Parkinson's disease. Yet, next to nothing is known about their specific stemness characteristics. We therefore devised a study aiming to compare olfactory lamina propria stem cells from 4 individuals to bone marrow mesenchymal stem cells from 4 age- and gender-matched individuals. Using pangenomic microarrays and immunostaining with 34 cell surface marker antibodies, we show here that olfactory stem cells are closely related to bone marrow stem cells. However, olfactory stem cells also exhibit singular traits. By means of techniques such as proliferation assay, cDNA microarrays, RT-PCR, in vitro and in vivo differentiation, we report that when compared to bone marrow stem cells, olfactory stem cells display (1) a high proliferation rate; (2) a propensity to differentiate into osseous cells; and (3) a disinclination to give rise to chondrocytes and adipocytes. Since peripheral olfactory stem cells originate from a neural crest-derived tissue and, as shown here, exhibit an increased expression of neural cell-related genes, we propose to name them olfactory ectomesenchymal stem cells (OE-MSC). Further studies are now required to corroborate the therapeutic potential of OE-MSCs in animal models of bone and brain diseases.
Developmental Vitamin D Deficiency Alters Learning in C57Bl/6J Mice
Epidemiological studies have highlighted a season of birth effect in multiple sclerosis and schizophrenia. As a result, low prenatal vitamin D has been proposed as a candidate risk factor for these brain diseases, with cognitive impairments. In order to further investigate the long-term consequences of a transient gestational hypovitaminosis D, we used a mouse developmental vitamin D (DVD) deficiency model. Female C57Bl/6J mice were fed a vitamin D-free diet for 6 weeks prior to conception and during gestation. At birth, dams and their offspring were fed a normal vitamin D-containing diet. The adult offspring underwent a learning test based on olfactory cues, at 30 weeks and 60 weeks of age. In addition, using magnetic resonance imaging (MRI), volumes of cerebrum, hippocampus and lateral ventricles were measured at 30 weeks and 70 weeks of age. We found that DVD-deficient mice, when compared to control animals at Week 30, displayed impaired learning and smaller lateral ventricles. At Weeks 60-70, both groups deteriorated when compared to young mice and no significant difference was observed between groups. This study confirms that transient prenatal vitamin D deficiency alters brain development and functioning and induces cognitive impairments in the young adult offspring.
Targeted Gene Correction of Laminopathy-associated LMNA Mutations in Patient-specific IPSCs
Combination of stem cell-based approaches with gene-editing technologies represents an attractive strategy for studying human disease and developing therapies. However, gene-editing methodologies described to date for human cells suffer from technical limitations including limited target gene size, low targeting efficiency at transcriptionally inactive loci, and off-target genetic effects that could hamper broad clinical application. To address these limitations, and as a proof of principle, we focused on homologous recombination-based gene correction of multiple mutations on lamin A (LMNA), which are associated with various degenerative diseases. We show that helper-dependent adenoviral vectors (HDAdVs) provide a highly efficient and safe method for correcting mutations in large genomic regions in human induced pluripotent stem cells and can also be effective in adult human mesenchymal stem cells. This type of approach could be used to generate genotype-matched cell lines for disease modeling and drug discovery and potentially also in therapeutics.
Engraftment of Human Nasal Olfactory Stem Cells Restores Neuroplasticity in Mice with Hippocampal Lesions
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.
