Regeneration Of Sensory Cells Research Articles

Notch Prosensory Effects in the Mammalian Cochlea Are Partially Mediated by Fgf20

Hearing loss is becoming an increasingly prevalent problem affecting more than 250 million people worldwide. During development, fibroblast growth factors (FGFs) are required for inner ear development as well as hair cell formation in the mammalian cochlea and thus make attractive therapeutic candidates for the regeneration of sensory cells. Previous findings showed that Fgfr1 conditional knock out mice exhibited hair cell and support cell formation defects. Immunoblocking with Fgf20 antibody in vitro produced a similar phenotype. While hair cell differentiation in mice starts at embryonic day (E)14.5, beginning with the inner hair cells, Fgf20 expression precedes hair cell differentiation at E13.5 in the cochlea. This suggests a potential role for Fgf20 in priming the sensory epithelium for hair cell formation. Treatment of explants with a gamma-secretase inhibitor, DAPT, decreased Fgf20 mRNA, suggesting that Notch is upstream of Fgf20. Notch signaling also plays an early role in prosensory formation during cochlear development. In this report we show that during development, Notch-mediated regulation of prosensory formation in the cochlea occurs via Fgf20. Addition of exogenous FGF20 compensated for the block in Notch signaling and rescued Sox2, a prosensory marker, and Gfi1, an early hair cell marker in explant cultures. We hypothesized that Fgf20 plays a role in specification, amplification, or maintenance of Sox2 expression in prosensory progenitors of the developing mammalian cochlea.

175. Delivery Via Non-Viral Options to the Auditory Structures

Top of pageAbstract Nearly 50 million people in the US alone are affected by disorders of the inner ear making hearing loss one of the mose common neurodegenerative disorders. Recent studies have demonstrated a number of potential applications for gene therapy in the inner ear including regeneration of sensory cells. Most studies of gene transfer to the inner ear have used viral vectors. The flexibility and non toxic properties of non viral gene delivery systems may be ideal for the inner ear which is easily damaged by inflammation that may be associated with some viral vectors. We compared three types of delivery vehicles including cationic polyamines, dendrimers and liposomes carrying a GFP expressing plasmid driven by a hCMV promoter. Two separate delivery routes to the inner ear were used: Vectors were delivered via application to the round window or delivery into the cochlea via a fenestration of the utricle. We analyzed the distribution of GFP with the inner ear after delivery of varying concentrations of vector and plasmid. All vectors used delivered to the spiral ganglion cells. Delivery to hair cells was seen using cationic polyamine vectors. Overall these vectors appeared to deliver more efficiently, to the basal turn of the cochlea, suggesting that distribution within the fluid filled cochlea may be constrained by diffusion. Non viral gene transfer using advanced non viral vectors may provide a delivery system to the sensory hair cells and spiral ganglion cells. Options to modify viral vector systems for enhanced targeting may still provide better transfection rates.

664. Regeneration of Sensory Cells in the Inner Ear of Deafened Mature Guinea Pigs

Top of pageAbstract The mammalian organ of Corti, the sensory epithelium of the inner ear, is a mosaic composed of sensory cells (hair cells) and non- sensory supporting cells. All cells are highly differentiated in structure and function. Because no undifferentiated cells are held in reserve to replace damaged cells, hearing impairment due to loss of hair cells is permanent. Differentiation of complex tissues like the organ of Corti typically is governed by specific cascades of gene expression. In mice, a critical gene in the differentiation of hair cells is the basic helix-loop-helix transcription factor Atoh1(=Math1), a homolog of the Drosophila gene atonal. Previous studies have shown that inoculating inner ears of normal adult guinea pigs with an adenovirus vector expressing Math1 (Ad.Math1) can generate new cochlear hair cells in regions normally occupied only by supporting cells. In this study, we deafened adult guinea pigs by administration with ototoxic drugs (kanamycin and ethacrynic acid) prior to inoculating their inner ears with Ad.Math1 and evaluated differences in hair cell number and hearing thresholds before and after treatment.

Advances in the Hearing Sciences: Current Research and Clinical Applications

Advances in the Hearing Sciences: Current Research and Clinical Applications

Regeneration of sensory cells after laser ablation in the lateral line system: hair cell lineage and macrophage behavior revealed by time- lapse video microscopy

The regeneration of sensory hair cells in lateral line neuromasts of axolotls was investigated via nearly continuous time-lapse microscopic observation after all preexisting hair cells were killed by a laser microbeam. The laser treatments left neuromasts with one resident cell type, which was supporting cells. Over the course of 1 week, replacement hair cells arose either directly via differentiation of cells present in the epithelium from the beginning of the time-lapse period or via the development of cells produced after one or two divisions of supporting cells. All of the cell divisions that produced hair cells were asymmetrical. During the first hour after the treatment, macrophages and smaller leukocytes were attracted to the laser-treated neuromasts. The smaller leukocytes returned to control levels 48-60 hr after the treatment, whereas macrophages remained active there throughout the period of hair cell replacement. Macrophage incidence peaked 36-48 hr after the laser treatment. Macrophages phagocytosed damaged hair cells and supporting cells, as well as new cells and preexisting cells without recognizable damage. The results provide direct evidence of hair cells arising as progeny produced from the divisions of supporting cells, evidence of hair cells and supporting cells arising from the same cell division, evidence relating to the timing of hair cell differentiation, and indirect evidence pertaining to proposals that hair cells sometimes arise via conversion of cells without an intervening division. The results also suggest that macrophages may influence early stages in the process of hair cell regeneration.

2018 Regeneration of sensory cells in the vomeronasal epithelium of adult hamster

2018 Regeneration of sensory cells in the vomeronasal epithelium of adult hamster

The ultrastructure of the vomero-nasal organ in reptilia.

There are three types of cells in the vomero-nasal organ of Lacerta sicula and Natrix natrix: receptor cells, supporting cells and basal cells. The receptor cells bear microvilli and no cilia. In Lacerta centrioles are lacking, indicating that the ciliary apparatus can have no essential significance in the transducer process. In Natrix centrioles occur in the deeper dendritic region. The structural constituents of the dendrites are mitochondria, microtubules and characteristic vesicles the properties of which are described. The perikarya which have uniform structure send off axons of about 0.2 μ diameter. The supporting cells show signs of a very moderate secretory activity, which is different among the species investigated. The microvilli of the supporting cells are not distinguishable from those of the receptor cells. The dendrites of the latter are completely isolated by the apical parts of the supporting cells. The sheet-like processes of the supporting cells contain strands of tonofilaments and do not cover the perikarya of the receptor cells completely. Thus adjacent sensory cells or dendrites and sensory cells are separated among themselves only by the normal intercellular space. The ratio of sensory cells to supporting cells is about 7∶1. The basal cells resemble the supporting cells and replace these in the lower portion of the epithelium. The typical cellular junctions between sensory cells and supporting cells are described. There are no true tight junctions in the vomero-nasal sensory epithelium, and they are most probably absent from the nasal mucosa too. This absence would seem to indicate special conditions for cellular communication and the accessibility of the intercellular space for certain molecules. There is no sign of regeneration of sensory cells. Both immature blastema cells and degenerating receptor cells are not discernible.