A Mouse Model for Degeneration of the Spiral Ligament

Kada, Shinpei; Nakagawa, Takayuki; Ito, Juichi

doi:10.1007/s10162-008-0147-6

Cited by 20 publications

(18 citation statements)

References 29 publications

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“…A–C), while 3 mM 3‐NP application resulted in severe threshold shifts at day 1 after 3‐NP application (day 6 in Fig. D–F), similar to what was observed in our previous study (Kada et al, ). No significant recovery in the ABR thresholds was observed 6 days later, immediately before BMSC transplantation (pre in Fig.…”

Section: Resultssupporting

confidence: 89%

Bone Marrow Stromal Cells Accelerate Hearing Recovery via Regeneration or Maintenance of Cochlear Fibrocytes in Mouse Spiral Ligaments

Kada

Hamaguchi

Ito

et al. 2019

The Anatomical Record

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Mammalian cochleae have limited capacity for regeneration, which is one of the major difficulties in the treatment of sensorineural hearing loss. In the current study, we examined the potential of bone marrow‐derived stromal cells (BMSCs) for functional restoration of mouse cochleae through regeneration or maintenance of cochlear fibrocytes in the spiral ligament (SL). We used a mouse model of degeneration of cochlear fibrocytes in the SL using local application of 3‐nitropropionic acid (3‐NP), in which disruption of the gap junction network in the SL resulted in the reduction of the endocochlear potential (EP). Mouse BMSCs were infused into the posterior semicircular canal 7 days after 3‐NP application. Transplanted BMSCs were frequently observed in the cochlear fluid space 4 weeks after transplantation, although a few transplants had migrated into the cochlear tissues including the SL. BMSC‐treated cochleae exhibited higher cell densities in the SL and greater EP levels than the control ones. Immunohistochemistry further demonstrated the restoration of functional proteins in the SL. Significant recovery in thresholds of auditory brainstem responses following BMSC transplantation was found only at 40 kHz in a mild degeneration model. Our cumulative findings indicated that BMSCs accelerated regeneration or maintenance of fibrocytes in damaged SLs, leading to partial functional restoration of the mouse cochleae. Anat Rec, 303:478–486, 2020. © 2019 American Association for Anatomy

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Section: Resultssupporting

confidence: 89%

Bone Marrow Stromal Cells Accelerate Hearing Recovery via Regeneration or Maintenance of Cochlear Fibrocytes in Mouse Spiral Ligaments

Kada

Hamaguchi

Ito

et al. 2019

The Anatomical Record

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“…Under general anesthesia, ABR measurements were performed as previously described (Kada et al, 2009). Thresholds were determined at 4, 10, 20 and 40 kHz frequencies from a set of responses at varying intensities with 5-dB sound pressure level intervals.…”

Section: Abr Dpoaes and Endocochlear Potential Recordingmentioning

confidence: 99%

Hedgehog signaling regulates prosensory cell properties during the basal-to-apical wave of hair cell differentiation in the mammalian cochlea

et al. 2013

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SUMMARYMechanosensory hair cells and supporting cells develop from common precursors located in the prosensory domain of the developing cochlear epithelium. Prosensory cell differentiation into hair cells or supporting cells proceeds from the basal to the apical region of the cochleae, but the mechanism and significance of this basal-to-apical wave of differentiation remain to be elucidated. Here, we investigated the role of Hedgehog (Hh) signaling in cochlear development by examining the effects of up-and downregulation of Hh signaling in vivo. The Hh effector smoothened (Smo) was genetically activated or inactivated specifically in the developing cochlear epithelium after prosensory domain formation. Cochleae expressing a constitutively active allele of Smo showed only one row of inner hair cells with no outer hair cells (OHCs); abnormal undifferentiated prosensory-like cells were present in the lateral compartment instead of OHCs and their adjacent supporting cells. This suggests that Hh signaling inhibits prosensory cell differentiation into hair cells or supporting cells and maintains their properties as prosensory cells. Conversely, in cochlea with the Smo conditional knockout (Smo CKO), hair cell differentiation was preferentially accelerated in the apical region. Smo CKO mice survived after birth, and exhibited hair cell disarrangement in the apical region, a decrease in hair cell number, and hearing impairment. These results indicate that Hh signaling delays hair cell and supporting cell differentiation in the apical region, which forms the basal-to-apical wave of development, and is required for the proper differentiation, arrangement and survival of hair cells and for hearing ability.

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“…We also counted the numbers of beta‐III tubulin‐positive transplants, and calculated the ratio of beta‐III tubulin expressing transplants to total surviving transplants. In addition, the densities of SGNs in the Rosenthal canals were quantified in ouabain‐treated specimens as described previously 11. All data are presented as the mean ± 1 standard deviation.…”

Section: Methodsmentioning

confidence: 99%