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Stem Cells
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Stem cell investigations to assist regeneration of a range of other tissues have been reported. For example, surgery of the head and neck can lead to peripheral nerve damage, with the facial and recurrent laryngeal nerves (RLNs) most commonly affected. Muscle-derived MSCs have been shown to improve outcomes in RLN injuries and work with facial nerve injuries has shown that neural regeneration following axonotomy is enhanced by a combination of neural-induced MSCs and platelet-rich plasma.24 Interestingly, several regions of the nose act as sources of autologous stem cells, such as olfactory ensheathing cells, which assist neural and other regenerative procedures. Large deficiencies of the maxillofacial skeleton can result from traumatic damage, or resection following malignant invasion, and direct injection of MSCs, together with appropriate materials or scaffolds, can assist regeneration. Stem cells have also been discussed with regard to improvement in scars following surgery or trauma and there is a large body of literature that considers MSCs and scars.
The inherited basis of hypergonadotropic hypogonadism
Published in Philip E. Harris, Pierre-Marc G. Bouloux, Endocrinology in Clinical Practice, 2014
The transcription factor SOX10 plays an important role in the development of the neural crest and is involved in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation. Mutations in SOX10 have been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness. SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of findings of olfactory bulb agenesis in WS individuals, SOX10 was hypothesized to be also involved in KS. SOX10 loss-of-function mutations were found in approximately one third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a sub-population of glial cells called olfactory ensheathing cells. These mice showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs.81
Cellular Imaging of Cell Transplants
Published in Michel M. J. Modo, Jeff W. M. Bulte, Molecular and Cellular MR Imaging, 2007
Michel M.J. Modo, Jeff W.M. Bulte
Although this approach might be sufficient to monitor nonmigrating fetal grafts, cell transplants with a high migratory potential would not allow an acute assessment of distribution or overgrowth. At present, the use of contrast agents to prelabel transplanted cells is overcoming this issue. For instance, recently Lee et al.16 were able to detect SPIO-labeled olfactory ensheathing cells (OECs) for at least 2 months postinjection. OECs migrated in the intact spinal cord, but only showed limited migration in the damaged cord. The physical barrier of the transection severely limits the OECs’ ability to populate both sides of the stump. No behavioral improvement was observed in transplanted animals in comparison to lesioned animals. Transplantation of cells into both sides of the lesion might be needed to increase the functional repair mediated by cell transplantation. It was also observed that in lesioned animals, small hemorrhages resulted in hypointensities on the MR images. These small bleeds stained positive for Prussian Blue, a histochemical marker of iron often used to indicate the presence of iron oxide particles in transplanted cells. The use of an antidextran antibody7 that allows the immunohistochemical detection of dextran-chelated contrast agents provides a very selective approach to visualize only incorporated particles rather than an endogenous iron pool that can be found in macrophages. Similar issues arise for transplanted cells in the brain, where the injection of cells can easily damage small blood vessels and provide a source of false positives. The potential to develop specific imaging sequences, such as FIESTA, that are insensitive to hemorrhages but detect iron oxide particles might overcome these limitations.31
Nose-to-brain drug delivery for the treatment of Alzheimer’s disease: current advancements and challenges
Published in Expert Opinion on Drug Delivery, 2022
Prabakaran A, Mukta Agrawal, Mithun Rajendra Dethe, Hafiz Ahmed, Awesh Yadav, Umesh Gupta, Amit Alexander
The olfactory nerve pathway is a direct and primary route of drug transport from the nasal cavity to the brain. Based on the nature of drug and cellular structure there are two mechanisms of drug transport including intracellular and extracellular paths. The intracellular path utilizes olfactory neurons usually for lipophilic moieties, while extracellular passage of hydrophilic or polar drugs takes place through olfactory epithelial cells [18,19]. The intracellular passage is a slower mode of drug transport to the brain which takes around 24 h, it is also considered as intraneural path 3. The axonal end of olfactory neurons starts from the mucus layer of olfactory epithelium and ends in cells of the mitral valve at the olfactory bulb by crossing the cribriform plate of lamina propria. This region is filled with CSF, and neurons are surrounded by olfactory ensheathing cells. This olfactory nerve channel is expanded to other different regions of the brain like piriform cortex, anterior olfactory nucleus, olfactory bundle, and hypothalamus [20]. In intracellular transport, the drug is taken up by the neurons via endocytosis from the olfactory epithelial cells and then it passes through the nerve channels and enters the olfactory and other regions of the brain. Besides, transcellular pathway involves drug transfer through passive diffusion, receptor mediated endocytosis, fluid phase endocytosis, etc. This mode is suitable for the passage of highly lipophilic molecules.
Extracellular vesicles isolated from human olfactory ensheathing cells enhance the viability of neural progenitor cells
Published in Neurological Research, 2020
Olfactory ensheathing cells (OECs) are a unique type of glia present in the lamina propria of the olfactory mucosa, the outer layer of the olfactory bulb, and both inner and outer layers of the nerve fiber [1,2]. OECs ensheathe non-myelinated primary olfactory axons and enhance neural regeneration by migrating and promoting olfactory sensory axon extension from the nasal epithelium towards the olfactory bulb [3,4]. These cells sustain continuous axon extension and successful topographic targeting of olfactory receptor neurons. Numerous studies have demonstrated that OECs support neural regeneration by stimulating axonal myelination [5], secreting important survival factors for regenerated axons such as neurotrophic factors [6–8] and extracellular matrix (ECM) molecules [9–11], and regulating cell debris phagocytosis [12] and neuroinflammation [13]. Thus, these cells play critical roles in neurogenesis and neural regeneration, which are specific features of the mammalian olfactory system. Because of their distinctive properties and autologous origin, transplantation of OECs has emerged as an alternative potential therapy for repairing central nervous system (CNS) damage, particularly for spinal cord injury [14].
Emerging role of nanomedicine in the treatment of neuropathic pain
Published in Journal of Drug Targeting, 2020
Pankaj Bidve, Namrata Prajapati, Kiran Kalia, Rakesh Tekade, Vinod Tiwari
Embryonic stem cells are not used because of the ethical problem and also tumour-related risk. Neural stem cells are the most appropriate type of cells which can differentiate into neurons, astrocytes, and oligodendrocytes [86]. Silvia Franchiand colleagues in 2011 were first to use intravenous murine neural stem cells for the treatment of neuropathic pain. This group succeeded in elucidating the biochemical mechanism of neural stem cell therapy and suggested that these cells exert a bi-directional interaction with immune cells and modulatory factors induced by nerve lesion [87,88]. One of the mainproblems with this therapy was low survival rate in the host with a damaged spinal cord. Thus, this problem was overcome by using combinatorial strategy. Luo and colleagues found that co-transplantation of neural stem cells with olfactory ensheathing cells improved the sensory functions related to pain behaviour. The combinatorial strategy improved the axonal integrity and plasticity of ascending and descending pathways [88]. Neural stem cells isolated from both rodents as well as humans could be used for the cell therapy in neuropathic pain. Bone marrow derived mononuclear cells can also be used for the treatment of neuropathic pain [89].