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Miller, Sophie. "The development of olfactory ensheathing cells". Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709275.
Pełny tekst źródłaGoodman, Melba Nadine. "Interactions between olfactory bulb astrocytes, ensheathing cells and olfactory sensory neurons". Case Western Reserve University School of Graduate Studies / OhioLINK, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=case1060869724.
Pełny tekst źródłaKueh, J. L. L. "Clinical neural scaffold engineering for olfactory ensheathing cells". Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1346460/.
Pełny tekst źródłaFranceschini, Isabelle A. "Cellular and molecular studies on olfactory bulb ensheathing cells". Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301803.
Pełny tekst źródłaPerera, Surangi Nalika. "Olfactory ensheathing cell development : a transcriptome profiling approach". Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/288787.
Pełny tekst źródłaFjelldal, Marthe Fredheim. "Study of Rat Olfactory Ensheathing Cells in Alginate based Matrices". Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for bioteknologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-16803.
Pełny tekst źródłaCawardine, Darren Rhys. "Engineering canine olfactory ensheathing cells for spinal cord injury repair". Thesis, University of Bristol, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.738207.
Pełny tekst źródłaCameron, Nicholas John. "Developing Olfactory Ensheathing Cells for ex vivo Delivery of GDNF". Thesis, Griffith University, 2010. http://hdl.handle.net/10072/365205.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
Full Text
Wu, Ann Shang Medical Sciences Faculty of Medicine UNSW. "Olfactory ensheathing cells in a rat model of dorsal root injury". Awarded by:University of New South Wales. Medical Sciences, 2009. http://handle.unsw.edu.au/1959.4/44793.
Pełny tekst źródłaNazareth, Lynn. "Determining Cellular and Molecular Mechanisms Behind Glial Cell Phagocytosis". Thesis, Griffith University, 2021. http://hdl.handle.net/10072/408099.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Pharmacy & Med Sci
Griffith Health
Full Text
Lakatos, Andras. "Do olfactory ensheathing cells have advantages over Schwann cells in transplant mediated CNS repair?" Thesis, University of Glasgow, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274787.
Pełny tekst źródłaWood, Rachael Claire. "Bioprocess optimisation improves identity and potency of olfactory ensheathing cells for neurologic regeneration". Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10047503/.
Pełny tekst źródłaRayapureddi, S. "Characterisation and application of olfactory ensheathing cells for glaucoma induced optic nerve damage". Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1366899/.
Pełny tekst źródłaMcMonagle, Brent Anthony. "Nasal Derived Olfactory Ensheathing and Stem Cells in Peripheral Nerve Repair and Regeneration". Thesis, Griffith University, 2016. http://hdl.handle.net/10072/366095.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
Full Text
Choudhury, Indra N. "Enhancing therapeutic potential of olfactory ensheathing cells in spinal cord injury by phagocytosis". Thesis, Griffith University, 2023. http://hdl.handle.net/10072/421686.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Pharmacy & Med Sci
Griffith Health
Full Text
Sandvig, Ioanna. "The role of olfactory ensheathing cells, MRI, and biomaterials in transplant-mediated CNS repair". Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for sirkulasjon og bildediagnostikk, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-14639.
Pełny tekst źródłaWright, Alison Alexandra. "Olfactory Ensheathing Cell Behaviour and Interactions are Modulated by Secreted Products of OECs". Thesis, Griffith University, 2019. http://hdl.handle.net/10072/389563.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Full Text
Bianco, John I. "Stem Cells and Ensheathing Cells from the Nasal Olfactory Mucosa: a Tool for the Repair of the Damaged Spinal Cord". Thesis, Griffith University, 2008. http://hdl.handle.net/10072/368098.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Eskitis Institute for Cell and Molecular Therapies
Science, Environment, Engineering and Technology
Full Text
Westendorf, Kathryn A. "Brain lipid binding protein expression in lamina-propria olfactory ensheathing cells is regulated by delta/notch-like epidermal growth factor-related receptor". Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/3196.
Pełny tekst źródłaVukovic, Jana. "An in vitro and in vitro study on the role of the glycoprotein fibulin-3 in olfactory nerve growth and repair". University of Western Australia. School of Anatomy and Human Biology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0182.
Pełny tekst źródłaTechangamsuwan, Somporn. "Immortalization and proliferation of adult canine Schwann cells and olfactory ensheathing cells and their infection with canine distemper virus". Gießen : DVG-Service, 2009. http://d-nb.info/997318902/34.
Pełny tekst źródłaIbrahim, A. "The use of olfactory ensheathing cells to promote regeneration of axons of central nervous system neurons". Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1370619/.
Pełny tekst źródłaKeyvan-Fouladi, Naghmeh. "Functional repair of the corticospinal tract by delayed transplantation of olfactory ensheathing cells in adult rats". Thesis, Open University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402238.
Pełny tekst źródłaDe, Mello Thalles R. B. "Olfactory ensheathing glia : an investigation of factors affecting responsiveness of these cells in vitro and in vivo". University of Western Australia. School of Anatomy and Human Biology, 2006. http://theses.library.uwa.edu.au/adt-WU2006.0044.
Pełny tekst źródłaGranger, Nicolas. "Effects of intraspinal transplantation of mucosal olfactory ensheathing cells in chronic spinal cord injury in domestic dogs". Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608161.
Pełny tekst źródłaAmaya, Daniel Alejandro. "Integration of the Peripheral and Central Nervous System During Development of the Murine Olfactory Nerve". Thesis, Griffith University, 2016. http://hdl.handle.net/10072/367158.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
Full Text
Reshamwala, Ronak S. "Novel Surgical Approaches for Transplanting Three-Dimensional Constructs of Olfactory Ensheathing Cells to Repair the Injured Spinal Cord". Thesis, Griffith University, 2020. http://hdl.handle.net/10072/395103.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
Full Text
Tello, Velasquez Johana Paola. "Identification of Natural Compounds that Regulate Glial Cell Proliferation and Migration for Spinal Cord Injury Transplantation Purposes". Thesis, Griffith University, 2016. http://hdl.handle.net/10072/366849.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
Full Text
[Verfasser], Somporn Techangamsuwan. "Immortalization and proliferation of adult canine Schwann cells and olfactory ensheathing cells and their infection with canine distemper virus / by Somporn Techangamsuwan". Gießen : DVG-Service, 2009. http://d-nb.info/997318902/34.
Pełny tekst źródłaSarwat, Mariah. "Peptide functionalised hydrogels for tissue regeneration". Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/157715/1/Mariah_Sarwat_Thesis.pdf.
Pełny tekst źródłaWalkden, Heidi. "Bacterial infection of the brain: how bacteria penetrate the CNS by invading peripheral nerves". Thesis, Griffith University, 2020. http://hdl.handle.net/10072/395110.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Full Text
Kalincik, Tomas Medical Sciences Faculty of Medicine UNSW. "Disturbances of autonomic functions in spinal cord injury: autonomic dysreflexia and thermoregulation". Publisher:University of New South Wales. Medical Sciences, 2009. http://handle.unsw.edu.au/1959.4/43516.
Pełny tekst źródłaChen, Mo. "Natural products and glial cell therapy for repairing the nervous system". Thesis, Griffith University, 2019. http://hdl.handle.net/10072/389731.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
Full Text
Mayeur, Anne. "Role de la protéine ADAMTS 4 sur la repousse nerveuse centrale induite par les cellules gliales olfactives in vivo chez la souris. Potential of olfactory ensheathing cells from different sources for spinal cord repair Inhibition of ADAMTS-4 Expression in Olfactory Ensheathing Cells Enhances Recovery after Transplantation within Spinal Cord Injury". Thesis, Normandie, 2020. http://www.theses.fr/2020NORMR003.
Pełny tekst źródłaA spinal cord injury (SCI) induces a permanent sensorimotor impairment below the injury level. To date, a wide variety of cells have been used as biotherapy to treat spinal cord injuries in different animal models. Olfactory ensheathing cells (OECs) are one of the most promising. Indeed, OECs have been shown to improve recovery in many animal studies, as well as in patients (Phase I/IIa trials). However, it has been reported that the level of recovery significantly varies among patients. Therefore, it is essential to improve the regenerative efficiency of OECs. Recently, inhibition of the expression of ADAMTS 4 (a metalloprotease known to bind and degrade chondroitin sulfate proteoglycans) in glial cells in vitro has been shown to increase their synthesis of neurotrophic factors. In our team, we have already demonstrated that OECs produce ADAMTS 4 in vitro. We hypthesized that the expression of neurotrophic factors secreted by OECs can be increased by the suppression of ADAMTS 4. We studied their regenerative potential after spinal cord injury in mice. Our results show that ADAMTS 4/KO bulb primary OECs cultures upregulate their trophic factors’ expression in vitro, and that transplanting these same cells into a severe SCI increases functional recovery and tissue repair in vivo
Münchhoff, Maximilian [Verfasser], Bernhard [Akademischer Betreuer] Meyer i Thomas Rudolf [Akademischer Betreuer] Tölle. "Evaluating the viability of Olfactory Ensheathing Cells transduced to overexpress Glial Cell Line Derived Neurotrophic Factor in a rat model of Dorsal Root Injury / Maximilian Münchhoff. Gutachter: Thomas Rudolf Tölle. Betreuer: Bernhard Meyer". München : Universitätsbibliothek der TU München, 2012. http://d-nb.info/1022885677/34.
Pełny tekst źródłaGeller, Sarah. "Caractérisation des cellules gliales olfactives associées aux neurones à GnRH-I : rôle dans le développement de ces neurones". Thesis, Tours, 2013. http://www.theses.fr/2013TOUR4011/document.
Pełny tekst źródłaGnRH-I cells control reproduction functions in mammals. These cells are extra cerebral since they come from the nasal pit and migrate to the forebrain during embryonic development. Numerous studies have described the influence of different molecules on the migration of GnRH-1 neurons, however, the role of microenvironment cells remains poorly understood. Considering the role of glial cells in the forebrain’s neuronal migration, we had hypothesized that extra-cerebral GnRH-I neurons possess a glial environment necessary for their migration from the nose to the brain. Our results demonstrated that 1) GnRH-I neurons are associated with glial cells during their migration in the nasal septum and forebrain 2) These glial cells are progenitors of olfactory ensheathing cells, and differentiated within the rostral regions during neuronal migration. 3) These cells express genes encoding factors involved in GnRH-I neurons migration 4) Glial cells transcriptome are disrupted with estrogen-mimicking endocrine disruptor, and affects gene families involved in cell adhesion molecules necessary for migration and activity regulation of GnRH-I neurons
Chalfouh, Chaima. "Effet de la stimulation magnétique répétitive trans-spinale comme thérapie non invasive dans le cadre des lésions médullaires. The Regenerative Effect of Trans-spinal Magnetic Stimulation After Spinal Cord Injury: Mechanisms and Pathways Underlying the Effect FoxJ1 regulates spinal cord development and is required for the maintenance of spinal cord stem cell potential Inhibition of ADAMTS-4 Expression in Olfactory Ensheathing Cells Enhances Recovery after Transplantation within Spinal Cord Injury Resident neural stem cells guarantee the regeneration promoted by bulbar olfactory ensheathing cell transplantation after spinal cord injury". Thesis, Normandie, 2020. http://www.theses.fr/2020NORMR099.
Pełny tekst źródłaSpinal cord injury (SCI) leads to a loss of sensitive and motor functions. Currently, there is no therapeutic intervention offering a complete recovery. Here, we report that repetitive trans-spinal magnetic stimulation (rTSMS) can be a noninvasive SCI treatment that enhances tissue repair and functional recovery. Several techniques including immunohistochemical, behavioral, cells cultures, and proteomics have been performed. Moreover, different lesion paradigms, such as acute and chronic phase following SCI in wild-type and transgenic animals at different ages (juvenile, adult, and aged), have been used. We demonstrate that rTSMS modulates the lesion scar by decreasing fibrosis and inflammation and increases proliferation of spinal cord stem cells. Our results demonstrate also that rTSMS decreases demyelination, which contributes to axonal regrowth, neuronal survival, and locomotor recovery after SCI. This research provides evidence that rTSMS induces therapeutic effects in a preclinical rodent model and suggests possible translation to clinical application in humans
Centenaro, Lígia Aline. "Transplante de lâmina própria olfatória e respiratória após lesão medular em ratos : implicações sobre a recuperação locomotora, hiperreflexia e regeneração axonal". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/117255.
Pełny tekst źródłaSpinal cord injury (SCI) results in an irreversible loss of function below the injury site. These permanent disabilities occur due to local neuronal death and loss of ascending and descending axons in the spinal cord. In attempt to create a favorable environment for the re-growth of injured axons, olfactory ensheathing cells (OECs) have been transplanted as a treatment strategy in animals submitted to different experimental models of SCI. However, a consensus on the efficacy of this cellular transplantation has yet to be reached. The main focus of the present study was explore the efficacy of olfactory lamina propria (OLP, graft containing OECs) or respiratory lamina propria (RLP, graft without OECs) when transplanted immediately, 2-week or 4-week after spinal cord transection. After 12 weeks of transplantation, animals with OLP and RLP grafts showed a subtle hindlimb motor improvement. Furthermore, the transplantation of OLP when performed immediately after injury reduced the withdrawal reflex over-responsiveness, while the implantation of this tissue 4 weeks post-injury produced a discrete frequency-dependent habituation of the Hoffman reflex (the electrical analogue of the classic tendon jerk reflex). In all therapeutic windows used, both lamina propria grafts produced comparable results for tissue sparing, fibers sprouting and re-growth of myelinated fibers at the lesion site, indicating that delayed transplantation approach does not seem to limit the regenerative effects. However, the myelinated fibers observed at the transection site of animals that received OLP 2 or 4 weeks after injury had a smaller myelinated fiber area, diameter and myelin sheath thickness when compared to those animals transplanted with RLP grafts in the same periods. The immediate transplantation of OLP and RLP also foster limited supraspinal axonal re-connection as shown by the presence of neurons stained by retrograde tracing in brainstem nuclei and in the somatosensory cortex. A larger number of 5-HT positive axons were found in the cranial stump of both lamina propria groups compared to the lesion and caudal regions. CGRP positive axons were present in considerable numbers at the SCI site. The locomotor recovery and axon reparative effects were limited and similar between groups transplanted at different times with OLP and RLP, suggesting that these results could not be exclusively related to OECs. In conclusion, a greater understanding of the restorative potential of these tissue grafts is necessary to strengthen the rationale for application of this treatment in humans.
Lee, I.-Hui. "On CNS injury and olfactory ensheathing cell engraftment strategies /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-551-8/.
Pełny tekst źródła冼振鋒 i Chun-fung Sin. "Olfactory ensheathing cell transplanation in spinal cord after contusion injury". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40738930.
Pełny tekst źródłaSin, Chun-fung. "Olfactory ensheathing cell transplanation in spinal cord after contusion injury". Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40738930.
Pełny tekst źródłaDombrowski, Mary A. "Sciatic nerve remyelination and nodal formation following olfactory ensheathing cell transplantation". Yale University, 2008. http://ymtdl.med.yale.edu/theses/available/etd-08092007-114648/.
Pełny tekst źródłaWitheford, Richter Miranda. "Olfactory ensheathing cell mediated mechanisms of neurite outgrowth and axon regeneration". Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/963.
Pełny tekst źródłaMurthy, Manjari. "Regulation of olfactory ensheathing cell development by the transcription factor Runx1". Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=117000.
Pełny tekst źródłaLes cellules olfactives engainantes (COE) sont une classe unique de cellules gliales dans le système olfactif. Elles possèdent certaines caractéristiques antigéniques et fonctionnelles des deux grandes classes de cellules gliales, soit les cellules de Schwann et les astrocytes. De plus, elles peuvent traverser la frontière entre le système nerveux central (SNC) et périphérique (SNP). Les contributions indispensables des COE à la régénération continuelle du système olfactif tout au long de la vie adulte font de ces cellules des candidats extrêmement prometteurs pour les thérapies de transplantation cellulaire pour la régénération du SNC. Toutefois, les études préliminaires ont généré des résultats variables, ce qui remet en question l'utilité thérapeutique des COE. Une telle variation dans les résultats pourrait être causée par l'hétérogénéité des COE. Cette explication est fondée sur l'hypothèse que seules certaines sous-populations de COE auraient le potentiel de régénérer et d'engainer les axones. Cependant, notre compréhension des fonctions et des propriétés moléculaires spécifiques aux sous-populations de COE est limitée, ce qui restreint l'exploitation de leur potentiel. Nous avons déjà établi que le facteur de transcription Runx1 est exprimé spécifiquement dans une population de cellules que nous croyons être les COE dans le bulbe olfactif. Ici, nous montrons que Runx1 est exprimé dans une sous-population de COE dans la région interne de la couche du nerf olfactif (CNO) et nous présentons une caractérisation moléculaire de ces cellules. Nous montrons aussi qu'une diminution du niveau de la protéine Runx1 chez la souris augmente de façon significative la prolifération des COE présomptives et des précurseurs de COE. De plus, nous montrons qu'il y a une diminution concomitante dans le nombre de COE qui ont atteint la maturité développementale. Finalement, nous présentons des évidences initiales qui suggèrent que Runx1 est impliqué dans l'organisation topologique des COE qui expriment Runx1 dans la région interne du CNO. Ces résultats soulèvent la possibilité que Runx1 est impliqué dans la spécification du destin cellulaire des COE. Nous fournissons donc une avenue pour l'exploration future des mécanismes moléculaires qui contrôlent l'acquisition de l'identité, la spécification et la fonction des sous-populations spécifiques de COE.
Mallek, Jennifer de Toledo. "Hyaluronic acid-olfactory ensheathing cell compositions for spinal cord injury nerve regeneration". [Gainesville, Fla.] : University of Florida, 2006. http://purl.fcla.edu/fcla/etd/UFE0015880.
Pełny tekst źródłaBocking, Sarah. "Role for the transcription factor AML1/Runx1 in Olfactory Ensheathing Cell development". Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=92380.
Pełny tekst źródłaLes mécanismes intrinsèques de regulation de transcription sont requis au développement de l'hétérogénéité cellulaire. Le runt-related gène, Runx1, est impliqué dans le développement des neurons de l'épithélium olfactif. Les buts de ce projet étaient de caractériser les cellules exprimant Runx1 dans les bulbes olfactifs (BO) et de déterminer la fonction de Runx1 dans ces cellules. Les cellules exprimant Runx1 forment un domaine défini dans une des couches superficielle du BO et dans le BO accessoire et ont été identifiées comme étant des "olfactory ensheathing cells" appartenant à la couche intérieure du nerf olfactif (iOECs). Les analyses des iOECs qui n'expriment pas Runx1 suggère une perturbation de leur distribution. L'expression ectopique de Runx1 dans les cultures primaires d'OECs a été associée à une réduction du nombre d'OECs proliferatives. Ces résultats démontrent que Runx1 est exprimé par les iOEC et modifie leur distribution par modulation négative de leur capacité proliférative.
Ould-Yahoui, Adlane. "Le système MMP/TIMP dans la croissance neuritique et la motilité des cellules souches de la muqueuse olfactive". Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX20672.
Pełny tekst źródłaThe matrix metalloproteinases (MMPs) belong to a growing family of Zn2+-dependent endopeptidases, secreted or membrane-bound (MT-MMP), which play a fundamental role in the cell signalling. The activity of the MMPs is regulated by their endogenous inhibitors, the tissue inhibitors of MMPs (TIMPs). The MMP / TIMP system regulates the cell-cell and cell-extracellular matrix interactions and modulates the cellular motility through the cleavage of protein components of the extracellular matrix, as well during physiological and pathological conditions.Our results suggest that TIMP-1 is implicated in the modulation of the neurite outgrowth and morphology of cortical neurons through the inhibition at least in part, of MMP-2 and not MMP-9. Afterward, we study of the system MMP / TIMP in the migration of the stem cells of olfactory ectomesenchymal stem cells (OE-MSCs). We show that gelatinases MMP-2 and MMP-9 as well as MT1-MMP, are involved in OE-MSCs migration. We also show that gelatinases are probably involved in neurotrophic properties of the OE-MSCs and olfactory ensheathing cells.Altogether, these results provide new evidences on the role of MMP/TIMP system in central nervous system post-lesional processes
Fairless, Richard. "A comparison of the molecular mechanisms involved in olfactory ensheathing cell and Schwann cell interactions with astrocytes". Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413375.
Pełny tekst źródłaGueye, Yatma. "Implication de MMP-2 dans les propriétés des cellules engainantes de la muqueuse olfactive et dans la réparation des lésions de la moelle épinière : études in vitro et in vivo". Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX20681.
Pełny tekst źródłaWhen the mammalian central nervous system is injured, a set of secondary reactions involving inflammation and reactive gliosis leads to the formation of a glial scar that inhibits axonal regeneration. In the case of a spinal cord lesion, the lack of effective repair of injured axonal networks can lead to paraplegia or quadriplegia. Today it is estimated that more than 2.5 million people are suffering from these handicaps worldwide, and there is as yet no validated treatment to improve the situation of patients. However, based on animal models, some molecular, cellular, and rehabilitation therapy approaches seem promising. Degradation of chondroitin sulfate proteoglycan (CSPG), the main inhibitory protein of the glial scar, by cleavage of either the protein core or side chains glycosaminoglycans, promotes axonal regeneration and leads to functional recovery. Studies have shown that the matrix metalloproteinase MMP-2 is capable of degrading the core protein of the CSPG. In addition, olfactory mucosa ensheathing cells (OECs) represent the most promising cell type for promoting axonal growth and functional recovery after spinal cord injury. However, the mechanisms underlying the regenerative properties of OECs remain essentially unknown. Here, we present our work in 2 parts. First, we show in vitro that: i) OECs in primary culture secrete high levels of active MMP-2; ii) both gelatinases, MMP-2 and MMP-9, have a vesicular Golgi-dependent secretion; iii) the distribution of vesicles containing the MMPs is linked to cytoskeleton and molecular motors distribution, which are probably involved in focused secretion of these molecules; iv) MMPs may have a nuclear distribution in OECs; v) MMP-2 plays a role in the migration of EOCs, an important process in their ability to repair nerve tissue. In the second part of my work, we evaluated whether the MMP-2 contributed to the beneficial effects of EOCs. We used an in vivo approach and we show for the first time, in an animal model of hemisection of the spinal cord, and using anatomical, electrophysiological analysis of locomotion approaches, that a chronic administration of recombinant MMP-2: i) increases the number and diameter of axons in the distal side of the site of injury; ii) restores the response-evoked H-reflex distal to the lesion site, iii) enhances the respiratory response to electrically-induced muscle fatigue, and iv) most importantly, improves the recovery of locomotion. All our work suggests that MMP-2, secreted by the EOCs, plays an important role in the recovery properties of these cells, when transplanted into spinal cord lesions, and that this MMP has a real therapeutic potential that remains to be explored
Honoré, Axel. "Effet des Cellules Gliales Olfactives issues des Bulbes Olfactifs sur les cellules souches épendymaires et leur progénie après une lésion médullaire". Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR060/document.
Pełny tekst źródłaThe spinal cord injuries (SCI) lead to the damages of the spinal cord or nerves and often cause permanent changes in body functions leading to the death. Cell therapies have raised great hope for regenerative medicine. Clinical data showed that the olfactory ensheathing cells (OECs) enhanced functional recovery after SCI and could be a very attractive therapeutic approach. Moreover, the discovery of a new endogenous resident stem cell population, lining the central canal of the spinal cord, named ependymal stem cells, represents a new hope for the therapy. This thesis analyzed the role of OECs transplantation, on the behaviour of ependymal stem cells since these cells, together with astrocytes and pericytes significantly contribute to the recovery of SCI. The use of the mouse model hFoxJ1-CreERT2::YFP (allowing to specifically follow the ependymal stem cells ant their progeny) showed that OECs increased in vitro the self-renewal potential of spinal cord stem cells and modified their differentiation pathway towards a neural type. In vivo, OECs transplantation significantly increases the proliferation of ependymal cells and their differenciation into hypo-reactive astrocytes leading to the formation of a beneficial environment to neuronal survival and the neurogenesis establishment. Our results also showed for the first time that OECs transplantation after SCI allows the generation of new neurons by non-ependymal cell-derived progenitors. These results represent a new hope in the establishment of therapeutic strategies for the treatment of SCI in humans