scholarly journals Why is olfactory neuroepithelium?

2021 ◽  
Vol 9 (4) ◽  
pp. 211-218
Author(s):  
Hongyun Huang
Keyword(s):  
Cell Types ◽  
Olfactory Ensheathing Cells ◽  
Placebo Control ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Double Blind ◽  
Olfactory Neurons ◽  
Olfactory Neuroepithelium ◽  
Ensheathing Cells ◽  
Local Functional

Currently, most cellular therapeutic effects for nervous diseases cannot be proven in a multicenter, randomized, double-blind placebo-control clinical trials, except for a few kinds of cells such as olfactory ensheathing cells. These cells show significant improvements in functional recovery and quality of life for patients with chronic ischemic stroke. Also, olfactory neuron transplantation has promising neurorestorative effects on patients with vascular dementia. Human olfactory neuroepithelium can spontaneously and sustainably regenerate or produce new olfactory neurons and glial cell types for decades or a lifetime. The neurorestorative mechanisms of olfactory ensheathing cells are well known; however, little is known about the neurorestorative mechanisms of olfactory neurons. Therefore, I hypothesize that the neurorestorative mechanisms of olfactory neurons after transplantation: (1) can well migrate where they are needed and become local functional neurons, as they need to compensate or replace; (2) must be regulated by some special molecular factors to elongate their axons, modulate or direct synapses to correctly recognize and connect the target cells, and integrate functions. Based on olfactory neuroepithelium cells displaying the special characterization, neurorestorative mechanisms, clinical therapeutic achievements, and hypotheses of effective mechanisms, they (olfactory ensheathing cells and olfactory neurons) may be the most efficient instruments of neurorestoration.

scholarly journals Olfactory ensheathing cells in chronic ischemic stroke: A phase 2, double-blind, randomized, controlled trial

2020 ◽  
Vol 8 (3) ◽  
pp. 182-193
Author(s):  
Yunliang Wang
Keyword(s):  
Ischemic Stroke ◽  
Olfactory Ensheathing Cells ◽  
Controlled Study ◽  
Cell Group ◽  
Placebo Control ◽  
Phase 2 ◽  
Double Blind ◽  
Assessment Scores ◽  
Ensheathing Cells

Olfactory ensheathing cells (OECs) have shown promising results for patients with neurologic diseases in non-double-blind, placebo control studies. Thirty patients with a unilateral ischemic stroke of more than a year were enrolled in a phase 2, multicenter, randomized, double-blind, and placebo-controlled cell therapy trial with a subsequent 12-month follow-up. The primary therapeutic objective has shown that after 12 months, there were significant differences in National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) assessment scores among the OEC group, Schwann cell group and placebo medium group at one-year follow-up. The second therapeutic objective found that there were significant differences in NIHSS, mRS, and BI assessment scores when comparing the endpoint data with the baseline data in the OEC group. There was neither hypersensitivity reaction nor adverse event. The results of this multicenter, randomized, double-blind, and placebo-controlled study indicate that injecting OECs into the olfactory sub-mucosa have neurorestorative effects, which can improve the quality of life for patients with chronic ischemic strokes without serious side effects.

Olfactory Ensheathing Cells Mediate Neuroplastic Mechanisms After Olfactory Training in Mouse Model

2019 ◽  
Vol 34 (2) ◽  
pp. 217-229 ◽  
Author(s):  
Boo-Young Kim ◽  
JuYeon Park ◽  
EuiJin Kim ◽  
ByungGuk Kim
Keyword(s):  
Olfactory System ◽  
Olfactory Receptors ◽  
Olfactory Ensheathing Cells ◽  
Control Group ◽  
Messenger Ribonucleic Acid ◽  
Beneficial Effects ◽  
Olfactory Neuroepithelium ◽  
Ensheathing Cells ◽  
Olfactory Training ◽  
Stimulation Of

Background Several studies have reported beneficial effects of olfactory training (OT) on the olfactory nervous system. However, the mechanisms underlying the regeneration of the olfactory system induced by OT are still under investigation. Objectives To determine the key mechanisms involved in the olfactory system recovery and to assess the neuroplastic effects of OT. Methods Thirty healthy female C57BL/6 mice were randomly allocated to 4 groups: control, n = 6; anosmia (no treatment), n = 8; OT, n = 8; and steroid treatment; n = 8. Except for the control group, mice were administered 3-methylindole. Anosmia was assessed using a food-finding test (FFT). The olfactory neuroepithelium was for histological examinations, gene ontology with pathway analyses, RNA, and protein studies. Results FFT was significantly reduced at 3 weeks in the OT mice versus steroids (78.27 s vs 156.83 s, P < .008) and controls (78.27 s vs 13.14 s, P < .003), although final outcome in the FFT was similar in these groups. Expression of olfactory and neurogenesis marker was higher in the olfactory neuroepithelium of the OT group than in the anosmia group without treatment. The mechanisms underlying olfactory regeneration might be related to early olfactory receptor stimulation, followed by neurotrophic factor stimulation of neuronal plasticity. Conclusion OT can improve olfactory function and accelerate olfactory recovery. The mechanisms underlying olfactory regeneration might be related to an initial stimulation of olfactory receptors followed by neurogenesis. Olfactory ensheathing cells might play an important role in olfactory regeneration following OT, based on the observed changes in messenger ribonucleic acid (mRNA) and protein expression, as well as the findings of the gene analysis.

scholarly journals Transplantation of sh-miR-199a-5p-Modified Olfactory Ensheathing Cells Promotes the Functional Recovery in Rats with Contusive Spinal Cord Injury

2020 ◽  
Vol 29 ◽  
pp. 096368972091617 ◽  
Author(s):  
Zhengchao Gao ◽  
Yingjie Zhao ◽  
Xijing He ◽  
Zikuan Leng ◽  
Xiaoqian Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Diffusion Tensor ◽  
Olfactory Ensheathing Cells ◽  
Luciferase Reporter ◽  
Therapeutic Effects ◽  
Protein Levels ◽  
Cord Injury ◽  
Ensheathing Cells

MicroRNAs (miRNAs) function as gene expression switches, and participate in diverse pathophysiological processes of spinal cord injury (SCI). Olfactory ensheathing cells (OECs) can alleviate pathological injury and facilitate functional recovery after SCI. However, the mechanisms by which OECs restore function are not well understood. This study aims to determine whether silencing miR-199a-5p would enhance the beneficial effects of the OECs. In this study, we measured miR-199a-5p levels in rat spinal cords with and without injury, with and without OEC transplants. Then, we transfected OECs with the sh-miR-199a-5p lentiviral vector to reduce miR-199a-5p expression and determined the effects of these OECs in SCI rats by Basso–Beattie–Bresnahan (BBB) locomotor scores, diffusion tensor imaging (DTI), and histological methods. We used western blotting to measure protein levels of Slit1, Robo2, and srGAP2. Finally, we used the dual-luciferase reporter assay to assess the relationship between miR-199-5p and Slit1, Robo2, and srGAP2 expression. We found that SCI significantly increased miR-199a-5p levels ( P < 0.05), and OEC transplants significantly reduced miR-199a-5p expression ( P < 0.05). Knockdown of miR-199a-5p in OECs had a better therapeutic effect on SCI rats, indicated by higher BBB scores and fractional anisotropy values on DTI, as well as histological findings. Reducing miR-199a-5p levels in transplanted OECs markedly increased spinal cord protein levels of Slit1, Robo2, and srGAP2. Our results demonstrated that transplantation of sh-miR-199a-5p-modified OECs promoted functional recovery in SCI rats, suggesting that miR-199a-5p knockdown was more beneficial to the therapeutic effects of OEC transplants. These findings provided new insights into miRNAs-mediated therapeutic mechanisms of OECs, which helps us to develop therapeutic strategies based on miRNAs and optimize cell therapy for SCI.

scholarly journals Survival and Integration of Transplanted Olfactory Ensheathing Cells are Crucial for Spinal Cord Injury Repair: Insights from the Last 10 Years of Animal Model Studies

2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 132S-159S ◽  
Author(s):  
Ronak Reshamwala ◽  
Megha Shah ◽  
James St John ◽  
Jenny Ekberg
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Three Dimensional ◽  
Cell Types ◽  
Olfactory Nerve ◽  
Olfactory Ensheathing Cells ◽  
Spinal Cord Regeneration ◽  
Key Factors ◽  
Cord Injury ◽  
Ensheathing Cells

Olfactory ensheathing cells (OECs), the glial cells of the primary olfactory nervous system, support the natural regeneration of the olfactory nerve that occurs throughout life. OECs thus exhibit unique properties supporting neuronal survival and growth. Transplantation of OECs is emerging as a promising treatment for spinal cord injury; however, outcomes in both animals and humans are variable and the method needs improvement and standardization. A major reason for the discrepancy in functional outcomes is the variability in survival and integration of the transplanted cells, key factors for successful spinal cord regeneration. Here, we review the outcomes of OEC transplantation in rodent models over the last 10 years, with a focus on survival and integration of the transplanted cells. We identify the key factors influencing OEC survival: injury type, source of transplanted cells, co-transplantation with other cell types, number and concentration of cells, method of delivery, and time of transplantation after the injury. We found that two key issues are hampering optimization and standardization of OEC transplantation: lack of (1) reliable methods for identifying transplanted cells, and (2) three-dimensional systems for OEC delivery. To develop OEC transplantation as a successful and standardized therapy for spinal cord injury, we must address these issues and increase our understanding of the complex parameters influencing OEC survival.

The Methodology of Controlled Trials of Acupuncture

1989 ◽  
Vol 6 (1) ◽  
pp. 9-13 ◽  
Author(s):  
C A Vincent
Keyword(s):  
Controlled Trial ◽  
Specific Effect ◽  
Control Group ◽  
Placebo Control ◽  
Controlled Trials ◽  
Control Procedure ◽  
Therapeutic Effects ◽  
Trial Methodology ◽  
Double Blind ◽  
Single Blind

The double-blind controlled trial methodology cannot be straightforwardly applied to trials of acupuncture. The double-blind condition, where the clinician is ignorant of the treatment allocation, cannot be sensibly maintained in trials of acupuncture or other physical treatments. The definition of an appropriate control group is also a difficult matter. The great majority of controlled trials of acupuncture so far conducted are seriously flawed by the use of a placebo control that itself has therapeutic effects. Recently more appropriate control groups have been developed, notably mock TENS, which is inert, and minimal acupuncture, which has only a very slight specific effect. As trials can only be single blind, if is especially important to monitor the adequacy of the control procedure, to ensure that it is perceived as being as effective as the true treatment. It is suggested that this can be achieved by assessing the: credibility of the two treatment procedures. Controlled trials of acupuncture should therefore be single blind, and employ a control condition that has no more than minimal specific effects, but is nevertheless seen as a credible, bona fide treatment by patients.

scholarly journals A pilot study of clinical cell therapies in Alzheimer’s disease

2021 ◽  
Vol 9 (4) ◽  
pp. 269-284
Author(s):  
Xiaoling Guo ◽  
Yunliang Wang ◽  
Yan Li ◽  
Yanqiu Liu ◽  
Ying Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Cell Therapy ◽  
Cell Types ◽  
Placebo Control ◽  
Clinical Dementia Rating ◽  
Olfactory Ensheathing Cell ◽  
Double Blind ◽  
Cell Therapies

Alzheimer’s disease (AD) is a neurodegenerative disease dominated by progressive cognitive dysfunction causing significant social, economic, and medical crises. Cell therapy has demonstrated favorable effects for AD. This pilot study examined the safety and neurorestorative effects of the olfactory ensheathing cell (OEC), olfactory neuron (ON), and Schwann cell (SC) on patients with AD. Seven patients with AD were enrolled in this two-center, randomized, double-blind, and placebo- controlled cell therapy study with a subsequent 12-month follow-up. We randomly assigned one or two participants in OEC, ON, and SC therapy or OEC combined with ON and placebo control. All enrolled patients were injected cells or medium into the olfactory sub-mucosa. They got an assessment of Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating before treatment and 1, 3, 6, 12 months after treatment. We performed MRI or CT scans before treatment and 12 months after treatment. After integrating the results from the three evaluation methods, all cell types showed better results than a placebo control. ON and SC seem to exhibit more vital potential neurorestorative ability to enhance or convert the neurological functions of patients with AD, and OEC may help AD patients keep neurological functions stable. In this pilot study, there was no adverse or side-effect event. The results of this study strongly suggest conducting a phase II clinical trial of ON, SC, and OEC therapy to prove their neurorestorative effect on patients with AD.

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