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Journal articles on the topic 'Olfactory stem cells'

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Author: Grafiati

Published: 4 June 2021

Last updated: 19 February 2023

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1

Galeano, Carlos, Zhifang Qiu, Anuja Mishra, Steven L. Farnsworth, Jacob J. Hemmi, Alvaro Moreira, Peter Edenhoffer, and Peter J. Hornsby. "The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System." Cell Transplantation 27, no. 3 (March 2018): 501–14. http://dx.doi.org/10.1177/0963689718754561.

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Intranasal administration is a promising route of delivery of stem cells to the central nervous system (CNS). Reports on this mode of stem cell delivery have not yet focused on the route across the cribriform plate by which cells move from the nasal cavity into the CNS. In the current experiments, human mesenchymal stem cells (MSCs) were isolated from Wharton’s jelly of umbilical cords and were labeled with extremely bright quantum dots (QDs) in order to track the cells efficiently. At 2 h after intranasal delivery in immunodeficient mice, the labeled cells were found under the olfactory epithelium, crossing the cribriform plate adjacent to the fila olfactoria, and associated with the meninges of the olfactory bulb. At all times, the cells were separate from actual nerve tracts; this location is consistent with them being in the subarachnoid space (SAS) and its extensions through the cribriform plate into the nasal mucosa. In their location under the olfactory epithelium, they appear to be within an expansion of a potential space adjacent to the turbinate bone periosteum. Therefore, intranasally administered stem cells appear to cross the olfactory epithelium, enter a space adjacent to the periosteum of the turbinate bones, and then enter the SAS via its extensions adjacent to the fila olfactoria as they cross the cribriform plate. These observations should enhance understanding of the mode by which stem cells can reach the CNS from the nasal cavity and may guide future experiments on making intranasal delivery of stem cells efficient and reproducible.

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2

Wetzig, Andrew, Alan Mackay-Sim, and Wayne Murrell. "Characterization of Olfactory Stem Cells." Cell Transplantation 20, no. 11-12 (December 2011): 1673–91. http://dx.doi.org/10.3727/096368911x576009.

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3

Roisen, F. J., K. M. Klueber, C. L. Lu, L. M. Hatcher, A. Dozier, C. B. Shields, and S. Maguire. "Adult human olfactory stem cells." Brain Research 890, no. 1 (January 2001): 11–22. http://dx.doi.org/10.1016/s0006-8993(00)03016-x.

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4

Ozdener, H., C. Di Poto, N. Rawson, L. K. Pannell, and J. N. Baraniuk. "Proteomics of the Olfactory Stem Cells." Journal of Allergy and Clinical Immunology 123, no. 2 (February 2009): S261. http://dx.doi.org/10.1016/j.jaci.2008.12.1009.

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5

McDonald, Cameron, Alan Mackay-Sim, Denis Crane, and Wayne Murrell. "Could Cells from Your Nose Fix Your Heart? Transplantation of Olfactory Stem Cells in a Rat Model of Cardiac Infarction." Scientific World JOURNAL 10 (2010): 422–33. http://dx.doi.org/10.1100/tsw.2010.40.

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This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiationin vitroand after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grownin vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP) in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins.

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6

Mollichella, Marie-Laure, Violaine Mechin, Dany Royer, Patrick Pageat, and Pietro Asproni. "Isolation and Characterization of Cat Olfactory Ecto-Mesenchymal Stem Cells." Animals 12, no. 10 (May 17, 2022): 1284. http://dx.doi.org/10.3390/ani12101284.

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The olfactory mucosa contains olfactory ecto-mesenchymal stem cells (OE-MSCs) which show stemness features, multipotency capabilities, and have a therapeutic potential. The OE-MSCs have already been collected and isolated from various mammals. The aim of this study was to evaluate the feasibility of collecting, purifying and amplifying OE-MSCs from the cat nasal cavity. Four cats were included in the study. Biopsies of olfactory mucosa were performed on anesthetized animals. Then, the olfactory OE-MSCs were isolated, and their stemness features as well as their mesodermal differentiation capabilities were characterized. Olfactory mucosa biopsies were successfully performed in all subjects. From these biopsies, cellular populations were rapidly generated, presenting various stemness features, such as a fibroblast-like morphology, nestin and MAP2 expression, and sphere and colony formation. These cells could differentiate into neural and mesodermal lineages. This report shows for the first time that the isolation of OE-MSCs from cat olfactory mucosa is possible. These cells showed stemness features and multilineage differentiation capabilities, indicating they may be a promising tool for autologous grafts and feline regenerative medicine.

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7

Murrell, Wayne, François Féron, Andrew Wetzig, Nick Cameron, Karisha Splatt, Bernadette Bellette, John Bianco, Chris Perry, Gabriel Lee, and Alan Mackay-Sim. "Multipotent stem cells from adult olfactory mucosa." Developmental Dynamics 233, no. 2 (2005): 496–515. http://dx.doi.org/10.1002/dvdy.20360.

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8

Sacramento, S., S. Rebelo, and O. A. B. da Cruz e Silva. "Olfactory mucosa stem cells differentiate into neuron-like cells." Microscopy and Microanalysis 21, S6 (August 2015): 28–29. http://dx.doi.org/10.1017/s1431927614013816.

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9

Tomé, Mercedes, Susan L. Lindsay, John S. Riddell, and Susan C. Barnett. "Identification of Nonepithelial Multipotent Cells in the Embryonic Olfactory Mucosa." STEM CELLS 27, no. 9 (May 21, 2009): 2196–208. http://dx.doi.org/10.1002/stem.130.

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10

VanHook, Annalisa M. "Inflammation induces stem cell quiescence." Science Signaling 12, no. 605 (October 29, 2019): eaaz9665. http://dx.doi.org/10.1126/scisignal.aaz9665.

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11

Ercolin, Anna Carolina Mazeto, Kelly Cristine Santos Roballo, Juliana Barbosa Casals, Naira Caroline Godoy Pieri, Aline Fernanda Souza, Rodrigo da Silva Nunes Barreto, Fabiana Fernandes Bressan, et al. "Rabbit olfactory stem cells. Isolation protocol and characterization." Acta Cirurgica Brasileira 31, no. 1 (January 2016): 59–66. http://dx.doi.org/10.1590/s0102-865020160010000009.

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12

GAO, Liang, Li CAO, Zhi-da SU, Yan-ling ZHU, and Cheng HE. "Multipotency of cultured olfactory epithelium neural stem cells." Academic Journal of Second Military Medical University 29, no. 9 (December 30, 2009): 985–89. http://dx.doi.org/10.3724/sp.j.1008.2009.00985.

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13

Yoo, Shin Hyuk, Hae-Won Kim, and Jun Hee Lee. "Restoration of olfactory dysfunctions by nanomaterials and stem cells-based therapies: Current status and future perspectives." Journal of Tissue Engineering 13 (January 2022): 204173142210834. http://dx.doi.org/10.1177/20417314221083414.

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Dysfunction in the olfactory system of a person can have adverse effects on their health and quality of life. It can even increase mortality among individuals. Olfactory dysfunction is related to many factors, including post-viral upper respiratory infection, head trauma, and neurodegenerative disorders. Although some clinical therapies such as steroids and olfactory training are already available, their effectiveness is limited and controversial. Recent research in the field of therapeutic nanoparticles and stem cells has shown the regeneration of dysfunctional olfactory systems. Thus, we are motivated to highlight these regenerative approaches. For this, we first introduce the anatomical characteristics of the olfactory pathway, then detail various pathological factors related to olfactory dysfunctions and current treatments, and then finally discuss the recent regenerative endeavors, with particular focus on nanoparticle-based drug delivery systems and stem cells. This review offers insights into the development of future therapeutic approaches to restore and regenerate dysfunctional olfactory systems.

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14

Stepanova, O. V., E. K. Karsuntseva, G. A. Fursa, A. V. Chadin, M. P. Valikhov, A. P. Semkina, I. V. Reshetov, and V. P. Chekhonin. "OBTAINING OF CELLULAR PREPARATIONS OF RAT AND HUMAN OLFACTORY MUCOSA AND THEIR INFLUENCE ON THE SIZE OF MODELED SPINAL CORD CYSTALS." http://eng.biomos.ru/conference/articles.htm 1, no. 19 (2021): 75–77. http://dx.doi.org/10.37747/2312-640x-2021-19-75-77.

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Enriched cultures of olfactory ensheathing cells and neural stem/progenitor cells were obtained according to our developed protocols from the olfactory mucosa of rat and human. It has been shown that only transplantation of human and rat olfactory ensheathing cells leads to a significant decrease in the size of cysts, as well as their complete disappearance in some animals.

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15

Mackay-Sim, Alan. "Concise Review: Patient-Derived Olfactory Stem Cells: New Models for Brain Diseases." STEM CELLS 30, no. 11 (October 22, 2012): 2361–65. http://dx.doi.org/10.1002/stem.1220.

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16

Bagade, R. S., and DVNS Suresh. "A Transmission Electron Microscopic Study of the Olfactory Epithelium in Hill Stream Cyprinidiae, Garra mullya (Sykes)." International Journal of Forest, Animal And Fisheries Research 6, no. 4 (2022): 14–21. http://dx.doi.org/10.22161/ijfaf.6.4.3.

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Olfaction is primarily produced by the stimulation of receptor cells on the olfactory organ's neuroepithelial surface, surrounded by olfactory nerve fibres. Numerous fish life processes, including migration, communication, feeding, schooling, defence, and reproduction, depend heavily on olfactory signals and cues. The olfactory and reproductory systems are interconnected structurally and functionally, and puberty-related alterations in the olfactory epithelium are documented. The olfactory epithelium, which covers a large portion of the surface of the olfactory rosette, a structure found within the olfactory chambers on the fish rostrum, is where the olfactory receptor cells are situated. Although ultra structural transmission electron microscopic studies of the olfactory organ and bulb are carried out by some investigators but very sparse information is available on hillstream fishes and that is why this work has been undertaken to detail the structure of olfactory system in G. mullya by electron microscopy. Microvillous olfactory receptor cells are placed compactly adjacent to the supporting cell showing a junction complex : the zonula-ocludens. Polygonal white cells are present in between the basal cells and supporting cells. Small polyhedral basal cells lie just above the basal lamina of olfactory epithelium. Basal cells may be working as stem cells for regeneration of lost or damaged non sensory and goblet cells.

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17

Silva, Nuno A., Jeffrey M. Gimble, Nuno Sousa, Rui L. Reis, and António J. Salgado. "Combining Adult Stem Cells and Olfactory Ensheathing Cells: The Secretome Effect." Stem Cells and Development 22, no. 8 (April 15, 2013): 1232–40. http://dx.doi.org/10.1089/scd.2012.0524.

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18

Gomes, Eduardo D., Sofia S. Mendes, Rita C. Assunção-Silva, Fábio G. Teixeira, Ana O. Pires, Sandra I. Anjo, Bruno Manadas, et al. "Co-Transplantation of Adipose Tissue-Derived Stromal Cells and Olfactory Ensheathing Cells for Spinal Cord Injury Repair." STEM CELLS 36, no. 5 (February 5, 2018): 696–708. http://dx.doi.org/10.1002/stem.2785.

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19

Henkin, Robert Irwin, and Mona Abdelmeguid. "Action of Phosphodiesterase Inhibitors on Olfactory Epithelial Stem Cells." FASEB Journal 34, S1 (April 2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.02323.

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20

Viktorov, I. V., E. A. Savchenko, O. V. Ukhova, N. Yu Alekseyeva, and V. P. Chekhonin. "Multipotent stem and progenitor cells of the olfactory epithelium." Bulletin of Experimental Biology and Medicine 142, no. 4 (October 2006): 495–502. http://dx.doi.org/10.1007/s10517-006-0402-y.

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21

Lee, K., W. L. Fodor, and Z. Machaty. "55 INFLUENCE OF DONOR CELL TYPE ON THE DEVELOPMENT OF PORCINE NUCLEAR TRANSFER EMBRYOS." Reproduction, Fertility and Development 18, no. 2 (2006): 136. http://dx.doi.org/10.1071/rdv18n2ab55.

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Embryonic development after nuclear transfer is very low; the majority of cloned embryos do not survive the pre-implantation stage. Recent reports indicate that the characteristics of nuclear transfer embryos depend on the type of nuclear donor cells. It has been suggested that development after nuclear transfer improves if less differentiated cells are used as nuclear donors. The aim of the present study was to investigate the developmental potential of nuclear transfer embryos reconstructed using differentiated and non-differentiated cells. Two types of non-differentiated cells, skin stem cells and olfactory bulb progenitor cells, were used; fetal fibroblasts were used as differentiated control. Prior to nuclear transfer, the differentiated state of the cells was characterized by Oct-4 immunocytochemistry (Chemicon International, Inc., Temecula, CA, USA); Oct-4 is known to be expressed by pluripotent cells only. During nuclear transfer, the cells were transferred into the perivitelline space of in vitro-matured enucleated oocytes. After fusion, reconstructed oocytes were activated by an electrical pulse followed by incubation in 10 �g/mL cycloheximide and 5 �g/mL cytochalasin B for 5 h. The embryos were subsequently cultured in NCSU-23 medium for 6 days; their developmental data were recorded and compared by ANOVA. Non-differentiated cell types showed strong Oct-4 expression, whereas the marker protein was completely absent in fetal fibroblast cells. A total of 161 embryos were reconstructed using skin stem cells, 171 embryos from olfactory bulb progenitor cells, and 189 embryos from fibroblasts. Of the skin stem cell-derived embryos, 32.9% cleaved, and during subsequent culture, 5.6% developed to the morula/blastocyst stage. In the olfactory bulb progenitor cell group, 19.8% cleaved, and the percentage of embryos that developed to the morula/blastocyst stage was 4.7%. In the control group, 22.7% cleaved; the morula/blastocyst formation was 2.6%. Embryos reconstructed from skin stem cells showed superior cleavage rate compared to embryos from the other cell types (P < 0.05). Also, morula/blastocyst formation from skin stem cells was significantly higher than that from fetal fibroblasts (P < 0.05), and morula/blastocyst formation from olfactory bulb progenitor cell-derived embryos also tended to be higher compared to control embryos (P = 0.08). Furthermore, the formation of morulae/blastocysts per cleaved embryos was the highest in embryos reconstructed with olfactory bulb progenitor cells (23.5% vs. 17.0% using skin stem cells and 11.6% using fibroblasts) implying that embryos from olfactory bulb progenitor cells may have higher developmental potential in later stages of development. The results demonstrate that nuclei of different donor cells support development to various degrees and confirm previous reports that using non-differentiated cells as nuclear donors increases the efficiency of nuclear transfer in the pig.

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22

Choi, Sung S., Seung-Bin Yoon, Sang-Rae Lee, Sun-Uk Kim, Young Joo Cha, Daniel Lee, Seung U. Kim, Kyu-Tae Chang, and Hong J. Lee. "Establishment and Characterization of Immortalized Minipig Neural Stem Cell Line." Cell Transplantation 26, no. 2 (February 2017): 271–81. http://dx.doi.org/10.3727/096368916x692852.

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Despite the increasing importance of minipigs in biomedical research, there has been relatively little research concerning minipig-derived adult stem cells as a promising research tool that could be used to develop stem cell-based therapies. We first generated immortalized neural stem cells (iNSCs) from primary minipig olfactory bulb cells (pmpOBCs) and defined the characteristics of the cell line. Primary neural cells were prepared from minipig neonate olfactory bulbs and immortalized by infection with retrovirus carrying the v-myc gene. The minipig iNSCs (mpiNSCs) had normal karyotypes and expressed NSC-specific markers, including nestin, vimentin, Musashi1, and SOX2, suggesting a similarity to human NSCs. On the basis of the global gene expression profiles from the microarray analysis, neurogenesis-associated transcript levels were predominantly altered in mpiNSCs compared with pmpOBCs. These findings increase our understanding of minipig stem cells and contribute to the utility of mpiNSCs as resources for immortalized stem cell experiments.

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23

Brann, David H., Tatsuya Tsukahara, Caleb Weinreb, Marcela Lipovsek, Koen Van den Berge, Boying Gong, Rebecca Chance, et al. "Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia." Science Advances 6, no. 31 (July 24, 2020): eabc5801. http://dx.doi.org/10.1126/sciadv.abc5801.

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Abstract:Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

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24

Pandit, Sonali R., Jeremy M. Sullivan, Viktoria Egger, Alexander A. Borecki, and Sharon Oleskevich. "Functional Effects of Adult Human Olfactory Stem Cells on Early-Onset Sensorineural Hearing Loss." STEM CELLS 29, no. 4 (April 2011): 670–77. http://dx.doi.org/10.1002/stem.609.

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25

Alizadeh, Rafieh, Farnaz Ramezanpour, Amirhossein Mohammadi, Mina Eftekharzadeh, Sara Simorgh, Milad Kazemiha, and Fatemeh Moradi. "Differentiation of human olfactory system‐derived stem cells into dopaminergic neuron‐like cells: A comparison between olfactory bulb and mucosa as two sources of stem cells." Journal of Cellular Biochemistry 120, no. 12 (July 11, 2019): 19712–20. http://dx.doi.org/10.1002/jcb.29277.

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26

Melrose, James. "Fractone Stem Cell Niche Components Provide Intuitive Clues in the Design of New Therapeutic Procedures/Biomatrices for Neural Repair." International Journal of Molecular Sciences 23, no. 9 (May 5, 2022): 5148. http://dx.doi.org/10.3390/ijms23095148.

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The aim of this study was to illustrate recent developments in neural repair utilizing hyaluronan as a carrier of olfactory bulb stem cells and in new bioscaffolds to promote neural repair. Hyaluronan interacts with brain hyalectan proteoglycans in protective structures around neurons in perineuronal nets, which also have roles in the synaptic plasticity and development of neuronal cognitive properties. Specialist stem cell niches termed fractones located in the sub-ventricular and sub-granular regions of the dentate gyrus of the hippocampus migrate to the olfactory bulb, which acts as a reserve of neuroprogenitor cells in the adult brain. The extracellular matrix associated with the fractone stem cell niche contains hyaluronan, perlecan and laminin α5, which regulate the quiescent recycling of stem cells and also provide a means of escaping to undergo the proliferation and differentiation to a pluripotent migratory progenitor cell type that can participate in repair processes in neural tissues. Significant improvement in the repair of spinal cord injury and brain trauma has been reported using this approach. FGF-2 sequestered by perlecan in the neuroprogenitor niche environment aids in these processes. Therapeutic procedures have been developed using olfactory ensheathing stem cells and hyaluronan as a carrier to promote neural repair processes. Now that recombinant perlecan domain I and domain V are available, strategies may also be expected in the near future using these to further promote neural repair strategies.

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27

Lee, IL-Woo, Hyun-Sun Lee, Jin-Sup Jung, Hee-Young Park, and Hwan-Jung Roh. "Isolation of Neural Stem Cells from the Subventricular Zone and the Olfactory Bulb of Neonatal Mice." Journal of Clinical Otolaryngology Head and Neck Surgery 15, no. 2 (November 2004): 227–33. http://dx.doi.org/10.35420/jcohns.2004.15.2.227.

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28

Tian, Jie, Qiugang Zhu, Ke Rui, Liwei Lu, and Shengjun Wang. "Mesenchymal stem cells derived exosomes promote the expansion of Bregs and alleviate the collagen-induced arthritis." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 237.19. http://dx.doi.org/10.4049/jimmunol.204.supp.237.19.

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Abstract Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a population of cells which has been recognized as a novel resident stem cell type in the olfactory lamina propria. OE-MSCs have been shown to exert their immunosuppressive capacity by modulating T cell responses. However, it remains unclear whether OE-MSCs possess any immunoregulatory functions on regulatory B cells (Bregs). Exosomes are secreted nanosized membrane vesicles that are increasingly implicated as an important communication tool among various cell types. In this study, exosomes derived from olfactory ecto-mesenchymal stem cells (OE-MSCs-Exo) effectively enhanced the proportions of CD19+IL-10+ Bregs in the spleen and draining lymph nodes, thus suppressing the development of collagen-induced arthritis (CIA). In culture, OE-MSCs-Exo could significantly promote the differentiation and expansion of CD19+IL-10+ Bregs, and the further investigation demonstrated that the expansion of Bregs was orchestrated by Ebi3 secreted by exosomes. Taken together, OE-MSCs-Exo have the potential to alleviate the severity of CIA through inducing Bregs, indicating OE-MSCs-Exo may represent a new therapeutic strategy for the treatment of rheumatoid arthritis.

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29

Shouman,, Z., A. Abd-Elmaksoud,, S. Lashen, and Hany Marei. "DIFFERENTIATION OF HUMAN OLFACTORY BULB NEURAL STEM CELLS INTO OLIGODENDROCYTES." Mansoura Veterinary Medical Journal 18, no. 1 (December 12, 2017): 195–207. http://dx.doi.org/10.21608/mvmj.2017.125683.

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30

Yusta-Boyo, Maria J., Manuel A. Gonzalez, Nancy Pavon, Ana B. Martin, Ricardo de la Fuente, Javier Garcia-Castro, Flora de Pablo, Rosario Moratalla, Antonio Bernad, and Carlos Vicario-Abejon. "Absence of hematopoiesis from transplanted olfactory bulb neural stem cells." European Journal of Neuroscience 19, no. 3 (February 2004): 505–12. http://dx.doi.org/10.1111/j.1460-9568.2004.03140.x.

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31

Vollrath, Michael, and Michael Altmannsberger. "Chemically Induced Esthesioneuroepithelioma: Ultrastructural Findings." Annals of Otology, Rhinology & Laryngology 98, no. 4 (April 1989): 256–66. http://dx.doi.org/10.1177/000348948909800404.

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Tumors of the olfactory epithelium of rats were induced with two different nitrosamines: 2,6-dimethylnitrosomorpholine and N-nitrosopiperidine. Both carcinogens yielded identical tumors consisting of small, undifferentiated, neuroblastic cell elements without specialized cell contact. Cell processes contained microtubuli, centrioles, and neurosecretory granules. Two kinds of rosettes were encountered frequently: Neuroblastic Homer Wright rosettes consisted of undifferentiated cells, surrounding a minute lumen filled with amorphous material; and Flexner rosettes showed a higher degree of maturation. Inside their central lumen, cell processes with characteristic features of olfactory sensory cells (basal bodies, cilia, centrioles, microtubuli) could be demonstrated. The stem cell of this tumor is most likely the undifferentiated light basal cell inside the olfactory epithelium, since its ultrastructural appearance and its cytoskeleton are alike. At least under neoplastic conditions, this stem cell may likewise differentiate into epithelial cells, since transition to squamous cell carcinomas has been observed. In view of their overwhelming similarity to their human counterpart, the induced tumors are most likely to represent esthesioneuroepitheliomas.

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32

Alvites, Rui D., Mariana V. Branquinho, Ana C. Sousa, Bruna Lopes, Patrícia Sousa, Justina Prada, Isabel Pires, et al. "Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration." Biomolecules 12, no. 6 (June 11, 2022): 818. http://dx.doi.org/10.3390/biom12060818.

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Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

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33

Sethi, Rosh, Roshan Sethi, Andy Redmond, and Erin Lavik. "Olfactory Ensheathing Cells Promote Differentiation of Neural Stem Cells and Robust Neurite Extension." Stem Cell Reviews and Reports 10, no. 6 (July 5, 2014): 772–85. http://dx.doi.org/10.1007/s12015-014-9539-7.

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34

Alvites, Rui D., Mariana V. Branquinho, Ana R. Caseiro, Irina Amorim, Sílvia Santos Pedrosa, Alexandra Rêma, Fátima Faria, et al. "Rat Olfactory Mucosa Mesenchymal Stem/Stromal Cells (OM-MSCs): A Characterization Study." International Journal of Cell Biology 2020 (January 29, 2020): 1–21. http://dx.doi.org/10.1155/2020/2938258.

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Stem/stromal cell-based therapies are a branch of regenerative medicine and stand as an attractive option to promote the repair of damaged or dysfunctional tissues and organs. Olfactory mucosa mesenchymal stem/stromal cells have been regarded as a promising tool in regenerative therapies because of their several favorable properties such as multipotency, high proliferation rate, helpful location, and few associated ethical issues. These cells are easily accessible in the nasal cavity of most mammals, including the rat, can be easily applied in autologous treatments, and do not cope with most of the obstacles associated with the use of other stem cells. Despite this, its application in preclinical trials and in both human and animal patients is still limited because of the small number of studies performed so far and to the nonexistence of a standard and unambiguous protocol for collection, isolation, and therapeutic application. In the present work a validation of a protocol for isolation, culture, expansion, freezing, and thawing of olfactory mucosa mesenchymal stem/stromal cells was performed, applied to the rat model, as well as a biological characterization of these cells. To investigate the therapeutic potential of OM-MSCs and their eventual safe application in preclinical trials, the main characteristics of OMSC stemness were addressed.

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35

Morshead, C. M., C. G. Craig, and D. van der Kooy. "In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain." Development 125, no. 12 (June 15, 1998): 2251–61. http://dx.doi.org/10.1242/dev.125.12.2251.

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The adult mammalian forebrain contains a population of multipotential neural stem cells in the subependyma of the lateral ventricles whose progeny are the constitutively proliferating cells, which divide actively throughout life. The adult mammalian brain is ideal for examining the kinetics of the stem cells due to their strict spatial localization and the limited and discrete type of progeny generated (constitutively proliferating cells). Clonal lineage analyses 6 days after retrovirus infection revealed that under baseline conditions 60% of the constitutively proliferating cells undergo cell death, 25% migrate to the olfactory bulb and 15% remain confined to the lateral ventricle subependyma (where they reside for approximately 15 days). Analysis of single cell clones 31 days after retroviral infection revealed that the stem cell divides asymmetrically to self-renew and give rise to constitutively proliferating cells. Following repopulation of the depleted subependyma the average clone size is 2.8 times larger than control, yet the absolute number of cells migrating to the olfactory bulb is maintained and the stem cell retains its asymmetric mode of division. The number of neural stem cells in the adult forebrain 33 days after repopulation of the subependyma was estimated using bromodeoxyuridine labeling of subepenydmal cells. There were calculated to be 1200–1300 cells between the rostral corpus callosum and rostral anterior commissure; these data support a lineage model similar to those based on stem cell behavior in other tissue types.

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Sarnat, Harvey B., and Laura Flores-Sarnat. "Olfactory Development, Part 2: Neuroanatomic Maturation and Dysgeneses." Journal of Child Neurology 32, no. 6 (February 19, 2017): 579–93. http://dx.doi.org/10.1177/0883073816685192.

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Olfactory axons project from nasal epithelium to the primitive telencephalon before olfactory bulbs form. Olfactory bulb neurons do not differentiate in situ but arrive via the rostral migratory stream. Synaptic glomeruli and concentric laminar architecture are unlike other cortices. Fetal olfactory maturation of neuronal differentiation, synaptogenesis, and myelination remains incomplete at term and have a protracted course of postnatal development. The olfactory ventricular recess involutes postnatally but dilates in congenital hydrocephalus. Olfactory bulb, tract and epithelium are repositories of progenitor stem cells in fetal and adult life. Diverse malformations of the olfactory bulb can be diagnosed by clinical examination, imaging, and neuropathologically. Cellular markers of neuronal differentiation and synaptogenesis demonstrate immaturity of the olfactory system at birth, previously believed by histology alone to occur early in fetal life. Immaturity does not preclude function.

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Veron, Antoine D., Cécile Bienboire-Frosini, Stéphane D. Girard, Kevin Sadelli, Jean-Claude Stamegna, Michel Khrestchatisky, Jennifer Alexis, et al. "Syngeneic Transplantation of Olfactory Ectomesenchymal Stem Cells Restores Learning and Memory Abilities in a Rat Model of Global Cerebral Ischemia." Stem Cells International 2018 (2018): 1–10. http://dx.doi.org/10.1155/2018/2683969.

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Stem cells are considered as promising tools to repair diverse tissue injuries. Among the different stem cell types, the “olfactory ectomesenchymal stem cells” (OE-MSCs) located in the adult olfactory mucosa stand as one of the best candidates. Here, we evaluated if OE-MSC grafts could decrease memory impairments due to ischemic injury. OE-MSCs were collected from syngeneic F344 rats. After a two-step global cerebral ischemia, inducing hippocampal lesions, learning abilities were evaluated using an olfactory associative discrimination task. Cells were grafted into the hippocampus 5 weeks after injury and animal’s learning abilities reassessed. Rats were then sacrificed and the brains collected for immunohistochemical analyses. We observed significant impairments in learning and memory abilities following ischemia. However, 4 weeks after OE-MSC grafts, animals displayed learning and memory performances similar to those of controls, while sham rats did not improve them. Immunohistochemical analyses revealed that grafts promoted neuroblast and glial cell proliferation, which could permit to restore cognitive functions. These results demonstrated, for the first time, that syngeneic transplantations of OE-MSCs in rats can restore cognitive abilities impaired after brain injuries and provide support for the development of clinical studies based on grafts of OE-MSCs in amnesic patients following brain injuries.

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Chabrat, Audrey, Emmanuelle Lacassagne, Rodolphe Billiras, Sophie Landron, Amélie Pontisso-Mahout, Hélène Darville, Alain Dupront, et al. "Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons." Stem Cells International 2019 (May 19, 2019): 1–15. http://dx.doi.org/10.1155/2019/2945435.

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The discovery of novel drugs for neurodegenerative diseases has been a real challenge over the last decades. The development of patient- and/or disease-specific in vitro models represents a powerful strategy for the development and validation of lead candidates in preclinical settings. The implementation of a reliable platform modeling dopaminergic neurons will be an asset in the study of dopamine-associated pathologies such as Parkinson’s disease. Disease models based on cell reprogramming strategies, using either human-induced pluripotent stem cells or transcription factor-mediated transdifferentiation, are among the most investigated strategies. However, multipotent adult stem cells remain of high interest to devise direct conversion protocols and establish in vitro models that could bypass certain limitations associated with reprogramming strategies. Here, we report the development of a six-step chemically defined protocol that drives the transdifferentiation of human nasal olfactory stem cells into dopaminergic neurons. Morphological changes were progressively accompanied by modifications matching transcript and protein dopaminergic signatures such as LIM homeobox transcription factor 1 alpha (LMX1A), LMX1B, and tyrosine hydroxylase (TH) expression, within 42 days of differentiation. Phenotypic changes were confirmed by the production of dopamine from differentiated neurons. This new strategy paves the way to develop more disease-relevant models by establishing reprogramming-free patient-specific dopaminergic cell models for drug screening and/or target validation for neurodegenerative diseases.

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Tanos, Tamara, Alberto Maria Saibene, Carlotta Pipolo, Paolo Battaglia, Giovanni Felisati, and Alicia Rubio. "Isolation of putative stem cells present in human adult olfactory mucosa." PLOS ONE 12, no. 7 (July 18, 2017): e0181151. http://dx.doi.org/10.1371/journal.pone.0181151.

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Leung, Cheuk T., Pierre A. Coulombe, and Randall R. Reed. "Contribution of olfactory neural stem cells to tissue maintenance and regeneration." Nature Neuroscience 10, no. 6 (April 29, 2007): 720–26. http://dx.doi.org/10.1038/nn1882.

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Rustenhoven, Justin, and Jonathan Kipnis. "Smelling Danger: Olfactory Stem Cells Control Immune Defense during Chronic Inflammation." Cell Stem Cell 25, no. 4 (October 2019): 449–51. http://dx.doi.org/10.1016/j.stem.2019.09.006.

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Marei, Hany E., Zeinab Shouman, Asma Althani, Nahla Afifi, Abd-Elmaksoud A, Samah Lashen, Anwarul Hasan, et al. "Differentiation of human olfactory bulb-derived neural stem cells toward oligodendrocyte." Journal of Cellular Physiology 233, no. 2 (June 22, 2017): 1321–29. http://dx.doi.org/10.1002/jcp.26008.

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Covacu, Ruxandra, and Lou Brundin. "Effects of Neuroinflammation on Neural Stem Cells." Neuroscientist 23, no. 1 (July 7, 2016): 27–39. http://dx.doi.org/10.1177/1073858415616559.

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Neural stem/progenitor cells (NSCs/NPCs) are present in different locations in the central nervous system. In the subgranular zone (SGZ) there is a constant generation of new neurons under normal conditions. New neurons are also formed from the subventricular zone (SVZ) NSCs, and they migrate anteriorly as neuroblast to the olfactory bulb in rodents, whereas in humans migration is directed toward striatum. Most CNS injuries elicit proliferation and migration of the NSCs toward the injury site, indicating the activation of a regenerative response. However, regeneration from NSC is incomplete, and this could be due to detrimental cues encountered during inflammation. Different CNS diseases and trauma cause activation of the innate and adaptive immune responses that influence the NSCs. Furthermore, NSCs in the brain react differently to inflammatory cues than their counterparts in the spinal cord. In this review, we have summarized the effects of inflammation on NSCs in relation to their origin and briefly described the NSC activity during different neurological diseases or experimental models.

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Gazdic, Marina, Vladislav Volarevic, and Miodrag Stojkovic. "Stem Cells: New Hope For Spinal Cord Injury." Serbian Journal of Experimental and Clinical Research 16, no. 1 (March 1, 2015): 3–8. http://dx.doi.org/10.1515/sjecr-2015-0001.

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ABSTRACTStem cell therapy offers several attractive strategies for spinal cord repair. The regenerative potential of pluripotent stem cells was confirmed in an animal model of Spinal Cord Injury (SCI); nevertheless, optimized growth and differentiation protocols along with reliable safety assays should be established prior to the clinical application of hESCs and iPSCs. Th e therapeutic effects of mesenchymal stem cells (MSCs) in SCI result from neurotrophin secretion, angiogenesis, and antiinflammatory actions. Several preclinical SCI studies have reported that the occurrence of axonal extension, remyelination and neuroprotection occur after the transplantation of olfactory ensheathing cells (OECs). The transplantation of neural stem cells NSCs (NSCs) promotes partial functional improvement after SCI because of their potential to differentiate into neurons, oligodendrocytes, and astrocytes. The ideal source of stem cells for safe and efficient cell-based therapy for SCI remains a challenging issue that requires further investigation.

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Moreno-EstellÉs, Mireia, Pilar GonzÁlez-Gómez, Rafael Hortigüela, María Díaz-Moreno, Juana San Emeterio, Carvalho AL, Isabel FariÑas, and Helena Mira. "Symmetric Expansion of Neural Stem Cells from the Adult Olfactory Bulb Is Driven by Astrocytes Via WNT7A." STEM CELLS 30, no. 12 (November 27, 2012): 2796–809. http://dx.doi.org/10.1002/stem.1243.

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Kawabori, Masahito, Hideo Shichinohe, Satoshi Kuroda, and Kiyohiro Houkin. "Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke." International Journal of Molecular Sciences 21, no. 19 (October 6, 2020): 7380. http://dx.doi.org/10.3390/ijms21197380.

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Despite recent developments in innovative treatment strategies, stroke remains one of the leading causes of death and disability worldwide. Stem cell therapy is currently attracting much attention due to its potential for exerting significant therapeutic effects on stroke patients. Various types of cells, including bone marrow mononuclear cells, bone marrow/adipose-derived stem/stromal cells, umbilical cord blood cells, neural stem cells, and olfactory ensheathing cells have enhanced neurological outcomes in animal stroke models. These stem cells have also been tested via clinical trials involving stroke patients. In this article, the authors review potential molecular mechanisms underlying neural recovery associated with stem cell treatment, as well as recent advances in stem cell therapy, with particular reference to clinical trials and future prospects for such therapy in treating stroke.

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Tanaka, Aoi, Shohei Ishida, Takahiro Fuchigami, Yoshitaka Hayashi, Anri Kuroda, Kazuhiro Ikenaka, Yugo Fukazawa, and Seiji Hitoshi. "Life-Long Neural Stem Cells Are Fate-Specified at an Early Developmental Stage." Cerebral Cortex 30, no. 12 (August 6, 2020): 6415–25. http://dx.doi.org/10.1093/cercor/bhaa200.

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Abstract The origin and life-long fate of quiescent neural stem cells (NSCs) in the adult mammalian brain remain largely unknown. A few neural precursor cells in the embryonic brain elongate their cell cycle time and subsequently become quiescent postnatally, suggesting the possibility that life-long NSCs are selected at an early embryonic stage. Here, we utilized a GFP-expressing lentivirus to investigate the fate of progeny from individual lentivirus-infected NSCs by identifying the lentiviral integration site. Our data suggest that NSCs become specified to two or more lineages prior to embryonic day 13.5 in mice: one NSC lineage produces cells only for the cortex and another provides neurons to the olfactory bulb. The majority of neurosphere-forming NSCs in the adult brain are relatively dormant and generate very few cells, if any, in the olfactory bulb or cortex, and this NSC population could serve as a reservoir that is occasionally reactivated later in life.

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Rojas‐Mayorquín, Argelia Esperanza, Nadia Magali Torres‐Ruíz, Graciela Gudiño‐Cabrera, and Daniel Ortuño‐Sahagún. "Subtractive hybridization identifies genes differentially expressed by olfactory ensheathing cells and neural stem cells." International Journal of Developmental Neuroscience 28, no. 1 (September 20, 2009): 75–82. http://dx.doi.org/10.1016/j.ijdevneu.2009.08.019.

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Anna, Zadroga, Jezierska-Woźniak Katarzyna, Czarzasta Joanna, Monika Barczewska, Wojtkiewicz Joanna, and Maksymowicz Wojciech. "Therapeutic Potential of Olfactory Ensheathing Cells and Mesenchymal Stem Cells in Spinal Cord Injuries." Stem Cells International 2017 (2017): 1–6. http://dx.doi.org/10.1155/2017/3978595.

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Spinal cord injury (SCI) is a devastating neurological condition that affects individuals worldwide, significantly reducing quality of life, for both patients and their families. In recent years there has been a growing interest in cell therapy potential in the context of spinal cord injuries. The present review aims to discuss and compare the restorative approaches based on the current knowledge, available spinal cord restorative cell therapies, and use of selected cell types. However, treatment options for spinal cord injury are limited, but rehabilitation and experimental technologies have been found to help maintain or improve remaining nerve function in some cases. Mesenchymal stem cells as well as olfactory ensheathing cells seem to show therapeutic impact on damaged spinal cord and might be useful in neuroregeneration. Recent research in animal models and first human trials give patients with spinal cord injuries hope for recovery.

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Huang, Yuahn-Sieh, I.-Hsun Li, Sheau-Huei Chueh, Dueng-Yuan Hueng, Ming-Cheng Tai, Chang-Min Liang, Shiu-Bii Lien, Huey-Kang Sytwu, and Kuo-Hsing Ma. "Mesenchymal stem cells from rat olfactory bulbs can differentiate into cells with cardiomyocyte characteristics." Journal of Tissue Engineering and Regenerative Medicine 9, no. 12 (February 4, 2013): E191—E201. http://dx.doi.org/10.1002/term.1684.

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