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Light photomicrographs of control rat inner ear cavity demonstrating the cochlear cavity divided by Reissener's membrane (RM) into scala media (SM) and scala vestibule(SV). The organ of Corti (OC) intervenes between the scala media and the scala tympani (ST). It is bounded laterally by the stria vascularis (St V) and medially by the spiral ganglion (SG). The semicircular duct (SD) shows the macula utriculi (U) and the crista ampullaris (CA) (H&E stain. Mic. Mag. ×40).
Source publication
Background and Objectives
The utilization of the stem cells is widely used in the last few years in different fields of medicine, either by external transplantation or endogenous mobilization, most of these studies still experimental on animals; few were tried on human as in the spinal cord injury or myocardial infarction. As regard its use in the...
Contexts in source publication
Context 1
... negative control rats demonstrated a normal organ of Corti with typical structural organization (Fig. 1). The sensory epithelium was formed of hair cells arranged in an inner and several outer rows ( Fig. 2) with intact apical stereocilia (Fig. 7A). The normal arrangement of the rows of inner and outer hair cells was demonstrated in the pe- culiar architecture of the reticular lamina of the cochlea as seen by the SEM (Fig. ...
Context 2
... negative control rats demonstrated a normal organ of Corti with typical structural organization (Fig. 1). The sensory epithelium was formed of hair cells arranged in an inner and several outer rows ( Fig. 2) with intact apical stereocilia (Fig. 7A). The normal arrangement of the rows of inner and outer hair cells was demonstrated in the peculiar architecture of the reticular lamina of the cochlea as seen by the SEM (Fig. ...
Citations
... Chen et al. induced differentiation of human embryonic stem cells into hair-cell like cells and auditory neurons and displayed a mean auditory threshold reduction of 28.6 ± 3.6 dB when compared to controls [19]. Lastly, Elbana et al. demonstrated that granulocyte colony stimulating factor (GCSF) may mobilize endogenous bone marrow stem cells and positively shift DPOAE outcomes in rodent models of SNHL [20]. Collectively, these results suggest the promising role of MSCs for hearing loss. ...
Sensorineural hearing loss (SNHL) is the most common form of hearing loss that is routinely treated with hearing aids or cochlear implants. Advances in regenerative medicine have now led to animal studies examining the possibility of restoring injured hair cells with mesenchymal stem/stromal cell (MSC) administration. We conducted a systematic review and meta-analysis to collate the existing preclinical literature evaluating MSCs as a treatment for SNHL and quantify the effect of MSCs on functional hearing. Our protocol was published online on CAMARADES. Searches were conducted in four medical databases by two independent investigators. Twelve studies met inclusion and were evaluated for risk of bias using SYRCLE. Rodent models were commonly used (n = 8, 66%), while auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were the most frequent measures assessing hearing loss. MSCs were derived from multiple tissue sources, including bone marrow, adipose tissue, and umbilical cord blood and the dose ranged from 4 × 103 to 1 × 107 cells. Treatment with MSCs resulted in an improvement in ABR and DPOAE (mean difference-15.22, + 9.10, respectively). Despite high heterogeneity and multiple “unclear” domains in the risk of bias, this review provides evidence that MSCs may have a beneficial effect in hearing function.
... 15 In several articles, a combination of stem cell transplantation and the G-CSF has been utilized with a view to repairing various parts of the body. [16][17][18] Safari et al. 19 achieved fruitful results from combining BMSCs and the G-CSF to treat a rat model of Parkinson's disease. 19 Given that there have been no reports concerning the effects of the G-CSF on ovaries damaged by CTX, in the present study, for the first time, we evaluated the effects of the G-CSF on damaged ovaries after creating a chemotherapy model with CTX and compared the results with the effects of BMSC transplantation into ovaries and the effects of the coadministration of BMSCs and the G-CSF on ovaries damaged by chemotherapy in rats. ...
Background:
Bone marrow stromal cells (BMSCs), as a type of mesenchymal stem cells, and the granulocyte colony-stimulating factor (G-CSF), as a type of growth factor, may recover damaged ovaries. The aim of the present study was to investigate the effects of the coadministration of BMSCs and the G-CSF on damaged ovaries after creating a chemotherapy model with cyclophosphamide (CTX) in rats.
Methods:
The present study was performed in Semnan, Iran, in the late 2016 and the early 2017. BMSCs were cultured and were confirmed using the CD markers of stromal cells. Forty female Wistar rats were randomly divided into 4 groups. The rats were injected intraperitoneally with CTX for 14 days to induce chemotherapy and ovarian destruction. Then, the BMSCs were injected into bilateral ovaries and the G-CSF was injected intraperitoneally, individually and together. Four weeks later, the number of ovarian follicles using H&E staining, the number of apoptotic granulosa cells using the TUNEL assay, the number of produced oocytes from the ovaries, and the levels of serum E2 and FSH using an ELISA reader were assessed. Statistical analysis was done using one-way ANOVA with SPSS, version 16.0.
Results:
The results showed that the effects of the coadministration of 2×106 BMSCs and 70 µg/kg of the G-CSF were significantly more favorable than those in the control group (P<0.001), the BMSC group (P=0.016), and the G-CSF group (P<0.001) on the recovery of damaged ovaries.
Conclusion:
The efficacy of the coadministration of BMSCs and the G-CSF in the recovery of ovaries damaged by chemotherapy was high by comparison with the administration of either of them separately.
... 78 Likewise, following acute myocardial infarction, individuals with a higher baseline number of circulating stem cells showed a greater ejection fraction 6 months later. 79 A link between a lower number of circulating stem cells and the development of degenerative diseases has been established with diabetes, 80 Furthermore, increasing the number of circulating stem cells has been documented to enhance tissue repair or to improve the course of disease formation in cases of acute myocardial infarction, 93,94 stroke, 95 bone fracture, 96 muscle injury, 97 spinal cord injury, 98 diabetic wound healing, 99 and inner ear damage, 100 to name a few. Stem cell mobilization using an extract of the cyanophyta species Aphanizomenon flos-aquae was documented to improve cases of severe cardiomyopathy, stroke, diabetes, rheumatoid arthritis, kidney failure, and Parkinson's disease. ...
Purpose
The aim of this study was to evaluate the effects of a proanthocyanidin-rich extract of sea buckthorn berry (SBB-PE) on the numbers of various types of adult stem cells in the blood circulation of healthy human subjects.
Study design and methods
A randomized, double-blind, placebo-controlled, cross-over trial was conducted in 12 healthy subjects. Blood samples were taken immediately before and at 1 and 2 hours after consuming either placebo or 500 mg SBB-PE. Whole blood was used for immunophenotyping and flow cytometry to quantify the numbers of CD45dim CD34+ CD309+ and CD45dim CD34+ CD309− stem cells, CD45− CD31+ CD309+ endothelial stem cells, and CD45− CD90+ mesenchymal stem cells.
Results
Consumption of SBB-PE was associated with a rapid and highly selective mobilization of CD45dim CD34+ CD309− progenitor stem cells, CD45− CD31+ CD309+ endothelial stem cells, and CD45− CD90+ lymphocytoid mesenchymal stem cells. In contrast, only minor effects were seen for CD45dim CD34+ CD309+ pluripotential stem cells.
Conclusion
Consumption of SBB-PE resulted in selective mobilization of stem cell types involved in regenerative and reparative functions. These data may contribute to the understanding of the traditional uses of SBB for preventive health, regenerative health, and postponing the aging process.
... In the present study, we found that an EE prevents hippocampal damage caused by diabetes in a similar way as systemic injection of BM-MSCs [22]. A recent report showed that endogenous BM-MSCs stimulated with granulocyte colony stimulating factor increase the regeneration of damaged inner ear hair cells without injection of exogenous BM-MSCs [40]. Thus, we hypothesized that an EE has the potential to prevent cognitive impairment at least in part by activating endogenous BM-MSCs. ...
Increasing evidence suggests that an enriched environment (EE) ameliorates cognitive impairment by promoting repair of brain damage. However, the mechanisms by which this occurs have not been determined. To address this issue, we investigated whether an EE enhanced the capability of endogenous bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to prevent hippocampal damage due to diabetes by focusing on miRNA carried in BM-MSC-derived exosomes. In diabetic streptozotocin (STZ) rats housed in an EE (STZ/EE), cognitive impairment was significantly reduced, and both neuronal and astroglial damage in the hippocampus was alleviated compared with STZ rats housed in conventional cages (STZ/CC). BM-MSCs isolated from STZ/CC rats had functional and morphological abnormalities that were not detected in STZ/EE BM-MSCs. The miR-146a levels in exosomes in conditioned medium of cultured BM-MSCs and serum from STZ/CC rats were decreased compared with non-diabetic rats, and the level was restored in STZ/EE rats. Thus, the data suggest that increased levels of miR-146a in sera were derived from endogenous BM-MSCs in STZ/EE rats. To examine the possibility that increased miR-146a in serum may exert anti-inflammatory effects on astrocytes in diabetic rats, astrocytes transfected with miR-146a were stimulated with advanced glycation end products (AGEs) to mimic diabetic conditions. The expression of IRAK1, NF-κB, and tumor necrosis factor-α was significantly higher in AGE-stimulated astrocytes, and these factors were decreased in miR-146a-transfected astrocytes. These results suggested that EEs stimulate up-regulation of exosomal miR-146a secretion by endogenous BM-MSCs, which exerts anti-inflammatory effects on damaged astrocytes and prevents diabetes-induced cognitive impairment.
... Inner ear hair cells (HCs), primary transducers for perception of sound and balance, are not regenerated in mammals once they are lost (Hawkins et al., 1976;Schacht, 1986), thus replacement using various medical strategies, such as gene or cell therapy, is required to improve hearing ability (de Felipe et al., 2011;Qi et al., 2014;Hu and Ulfendahl, 2013;Okano and Kelley, 2012). Forced expression of the transcription factor Math1 (also known as Atoh1) via viral infection has been reported to generate new HCs in vivo (Kawamoto et al., 2003;Zheng and Gao, 2000;Staecker et al., 2014;Husseman and Raphael, 2009), while induction of HC-like cells from various stem cell sources has also been achieved using novel methods (McLean et al., 2016;Elbana et al., 2015;Hartman et al., 2015;Bramhall et al., 2014) and applied as translational therapy for individuals with hearing loss (Li et al., 2004;Oiticica et al., 2010;Xu et al., 2016;Barboza et al., 2016;Jongkamonwiwat et al., 2010). ...
We sought to establish a more efficient technique for induction of inner ear hair cell-like cells (HC-like cells) from embryonic stem cells (ES cells) by using a combination of two previously reported methods; ST2 stromal cell-conditioned medium, known to be favorable for HC-like cell induction (HIST2 method), and ES cells with transfer of the Math1 gene (Math1-ES cells). Math1-ES cells carrying Tet-inducible Math1 were cultured for 14days with doxycycline in conditioned medium from cultures of ST2 stromal cells following formation of 4-day embryoid bodies (EBs). Although each of the previously introduced methods have been reported to induce approximately 20% HC-like cells and 10% HC-like cells in their respective populations in EB outgrowths at the end of the culture periods, the present combined method was able to generate approximately 30% HC-like cells expressing HC-related markers (myosin6, myosin7a, calretinin, α9AchR, Brn3c), which showed remarkable formation of stereocilia-like structures. Analysis of expressions of marker genes specific for cochlear (Lmod3, Emcn) and vestibular (Dnah5, Ptgds) cells indicated that our HIST2 method may lead to induction of cochlear- and vestibular-type cells. In addition, continuous Math1 induction by doxycycline without use of the HIST2 method preferentially induced cochlear markers with negligible effects on vestibular marker induction.
Stem cells are derived from embryonic and non-embryonic tissues. Most stem cell studies are for animal stem cells and plants have also stem cell. Stem cells were discovered in 1981 from early mouse embryos. Stem cells have the potential to develop into all different cell types in the living body. Stem cell is a body repair system. When a stem cell divides it can be still a stem cell or become adult cell, such as a brain cell. Stem cells are unspecialized cells and can renew themselves by cell division, and stem cells can also differentiate to adult cells with special functions. Stem cells replace the old cells and repair the damaged tissues. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are thought to be limited to differentiating into different cell types of their tissue of origin. This article introduces recent research reports as references in the stem cell mobilization related studies.
Age-related hearing loss is the most common cause of adult auditory dysfunction. It is characterized by bilateral, progressive auditory deterioration associated with the aging process. There currently are limited options for the treatment as hearing aids or cochlear implants. To establish novel strategies for the treatment of this entity, it is crucial to elucidate the mechanisms of age-related hearing loss. Its etiology is believed to be multifactorial in-cluding both intrinsic and extrinsic factors. Oxidative damage, as seen in other aging organs systems, may play an essential role in the pathogenesis of the age-related hearing loss. Studies on animal models and human temporal bones have indicated a close relationship between degeneration of the cochlear lateral wall and hearing loss. Additional therapies that may prove beneficial in the treatment of age-related hearing loss include stem cell therapy, which we intend to review in this manuscript.
Hearing loss is present in millions of people worldwide. Current treatment for patients with severe to profound hearing loss consists of cochlear implantation. Providing the cochlear nerve is intact, patients generally benefit greatly from this intervention, frequently achieving significant improvements in speech comprehension. There are, however, some cases where current technology does not provide patients with adequate benefit. Ongoing research in cell transplantation and gene therapy promises to lead to new developments that will improve the function of cochlear implants. Translation of these experimental approaches is presently at an early stage. This review focuses on the application of biological therapies in severe hearing loss and discusses some of the barriers to translating basic scientific research into clinical reality. We emphasize the application of these novel therapies to cochlear implantation.
Mehrere Millionen Menschen weltweit leiden an Hörverlust. Derzeitige Therapien für Patienten mit hochgradigem Hörverlust beschränken sich auf die Versorgung mit einem Cochleaimplantat. Sofern der Hörnerv intakt ist, profitieren die behandelten Personen enorm, und ein Sprachverstehen ist wieder möglich. Allerdings gibt es nach wie vor Einschränkungen, die aus technologischer Sicht nicht angegangen werden. Neuartige Ansätze, basierend auf Zelltransplantation und Gentherapie, entwickeln sich rapide, zumindest im experimentellen Sektor. Klinische Translationsansätze indes sind, verglichen mit der Fülle an Grundlagenforschung auf diesem Gebiet, eher rudimentär. Die vorliegende Übersichtsarbeit konzentriert sich daher zum einen auf translationsfähige Ansätze und die zu überkommenden Hindernisse bei der Translation, zum anderen auf erste klinische Ansätze biologischer Therapien bei hochgradiger Schwerhörigkeit, insbesondere in Verbindung mit einer Cochleaimplantation.
Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear is comprised of a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them. In this article, we discuss recent advancements in understanding the pathways involved in auditory system signaling, from hair cell development through transmission to cortical centers. Our review discusses Notch and Wnt signaling, cell to cell communication through connexin and pannexin channels, and the detrimental effects of reactive oxygen species on the auditory system. There has been an increased interest in the auditory community to explore the signaling system in the ear for hair cell regeneration. Understanding signaling pathways in the auditory system will pave the way for the novel avenues to regenerate sensory hair cells and restore hearing function. This article is protected by copyright. All rights reserved.
