LGR5-Positive Supporting Cells Survive Ototoxic Trauma in the Adult Mouse Cochlea

Smith-Cortinez, Natalia; Yadak, Rana; Hendriksen, Ferry G. J.; Sanders, Eefje; Ramekers, Dyan; Stokroos, Robert J.; Versnel, Huib; Straatman, Louise V.

doi:10.3389/fnmol.2021.729625

Cited by 11 publications

(25 citation statements)

References 47 publications

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“…Recently, Smith-Cortinez et al reported the long-term presence of Lgr5+ SCs in the adult mouse cochlea ( Smith-Cortinez et al, 2021 ). These inner ear progenitor cells are able to survive in the cochlea even after severe ototoxic injury.…”

Section: Discussionmentioning

confidence: 99%

Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells

Ding

Cheng

et al. 2022

Front. Bioeng. Biotechnol.

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The ideal treatment for sensory hearing loss is to regenerate inner ear hair cells (HCs) through stem cell therapy, thereby restoring the function and structure of the cochlea. Previous studies have found that Lgr5+ supporting cells (SCs) in the inner ear can regenerate HCs, thus being considered inner ear progenitor cells. In addition to traditional biochemical factors, physical factors such as electrical conductivity also play a crucial role in the regulation of stem cell proliferation and differentiation. In this study, the graphene substrates were used to culture Lgr5+ progenitor cells and investigated their regulatory effects on cells. It was demonstrated that the graphene substrates displayed great cytocompatibility for Lgr5+ progenitors and promoted their sphere-forming ability. Moreover, more Myosin7a+ cells were found on the graphene substrates compared with tissue culture polystyrene (TCPS). These results suggest that graphene is an efficient interface that can promote the differentiation of Lgr5+ progenitors into HCs, which is great significance for its future application in combination with Lgr5+ cells to regenerate HCs in the inner ear.

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Section: Discussionmentioning

confidence: 99%

Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells

Ding

Cheng

et al. 2022

Front. Bioeng. Biotechnol.

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“…LGR4, LGR5, and LGR6 could be expressed in the cochlea (Zak et al, 2016;Zhang Y. et al, 2018;Smith-Cortinez et al, 2021). LGR5 is considered as a marker of cochlear stem cells and participates in the development of auditory HCs (Smith-Cortinez et al, 2021).…”

Section: Adenosine Receptorsmentioning

confidence: 99%

“…Another class of orphan receptors for Class A is one member of the leucine-rich repeat-containing G-protein-coupled receptors (LGRs) family. LGR4, LGR5, and LGR6 could be expressed in the cochlea ( Zak et al, 2016 ; Zhang Y. et al, 2018 ; Smith-Cortinez et al, 2021 ). LGR5 is considered as a marker of cochlear stem cells and participates in the development of auditory HCs ( Smith-Cortinez et al, 2021 ).…”

Section: Roles Of Class a G Protein-coupled Receptors In Cochleamentioning

confidence: 99%

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

Guo²,

Fu³

et al. 2022

Front. Mol. Neurosci.

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The prevalence of hearing loss-related diseases caused by different factors is increasing worldwide year by year. Currently, however, the patient’s hearing loss has not been effectively improved. Therefore, there is an urgent need to adopt new treatment measures and treatment techniques to help improve the therapeutic effect of hearing loss. G protein-coupled receptors (GPCRs), as crucial cell surface receptors, can widely participate in different physiological and pathological processes, particularly play an essential role in many disease occurrences and be served as promising therapeutic targets. However, no specific drugs on the market have been found to target the GPCRs of the cochlea. Interestingly, many recent studies have demonstrated that GPCRs can participate in various pathogenic process related to hearing loss in the cochlea including heredity, noise, ototoxic drugs, cochlear structure, and so on. In this review, we comprehensively summarize the functions of 53 GPCRs known in the cochlea and their relationships with hearing loss, and highlight the recent advances of new techniques used in cochlear study including cryo-EM, AI, GPCR drug screening, gene therapy vectors, and CRISPR editing technology, as well as discuss in depth the future direction of novel GPCR-based drug development and gene therapy for cochlear hearing loss. Collectively, this review is to facilitate basic and (pre-) clinical research in this area, and provide beneficial help for emerging GPCR-based cochlear therapies.

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“…In addition, limiting trauma opens the way for future developments relying on cochlear structure preservation, e.g. use of corticosteroids or neurotrophin eluting CIs, or hair cell regeneration 15 , 16 . Minimizing cochlear trauma during implantation can also reduce fibrosis and ossification on the long term making potential reimplantations easier to conduct 17 .…”

Section: Introductionmentioning

confidence: 99%

The effect of the surgical approach and cochlear implant electrode on the structural integrity of the cochlea in human temporal bones

Jwair

Versnel²,

Stokroos³

et al. 2022

Sci Rep

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Cochlear implants (CI) restore hearing of severely hearing-impaired patients. Although this auditory prosthesis is widely considered to be very successful, structural cochlear trauma during cochlear implantation is an important problem, reductions of which could help to improve hearing outcomes and to broaden selection criteria. The surgical approach in cochlear implantation, i.e. round window (RW) or cochleostomy (CO), and type of electrode-array, perimodiolar (PM) or lateral wall (LW), are variables that might influence the probability of severe trauma. We investigated the effect of these two variables on scalar translocation (STL), a specific type of severe trauma. Thirty-two fresh frozen human cadaveric ears were evenly distributed over four groups receiving either RW or CO approach, and either LW or PM array. Conventional radiological multiplanar reconstruction (MPR) was compared with a reconstruction method that uncoils the spiral shape of the cochlea (UCR). Histological analysis showed that RW with PM array had STL rate of 87% (7/8), CO approach with LW array 75% (6/8), RW approach with LW array 50% (4/8) and CO approach with PM array 29% (2/7). STL assessment using UCR showed a higher inter-observer and histological agreement (91 and 94% respectively), than that using MPR (69 and 74% respectively). In particular, LW array positions were difficult to assess with MPR. In conclusion, the interaction between surgical approach and type of array should be preoperatively considered in cochlear implant surgery. UCR technique is advised for radiological assessment of CI positions, and in general it might be useful for pathologies involving the inner ear or other complex shaped bony tubular structures.

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LGR5-Positive Supporting Cells Survive Ototoxic Trauma in the Adult Mouse Cochlea

Cited by 11 publications

References 47 publications

Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells

Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

The effect of the surgical approach and cochlear implant electrode on the structural integrity of the cochlea in human temporal bones

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