Journal Club: Graded response by Deiters' cells and Hensen's cells in the cochlea after ototoxic insult

on

Today's journal article

Ding D, Chen GD, Zhang C, Ye M, Adler HJ, Sharaf R, Naldrett K, Mittal T, Hu BH. Supporting cell involvement in cochlear damage and repair: Novel insights from a quantitative analysis of cyclodextrin-induced ototoxicity in mice. 

Why I picked this article

Sensorineural hearing loss occurs due to damage to the cochlea and the auditory nerve. Two primary cell types lost in sensorineural hearing loss are hair cells, our sensory cells that detect sounds, and auditory neurons, which propagate auditory information from the cochlea to the brain. The large majority of research has focused on the cell pathophysiology of hair cells and auditory neurons. This research publication, however, focuses on "supporting cells" which are literally thought to provide support for hair cells. 

"Supporting cell" is the name given to non-sensory cells on and surrounding the Organ of Corti. There are several different types of supporting cells: Dieters' cells, Piller cells, inner phalangeal cells, border cells, Hensen's cells, claudius cells, and Inner sulcus cells. Many of them have been reported to respond to cochlear injury. 

The present research focuses on understanding changes in supporting cells following cochlear injury using the mouse and ototoxic drug as the model for ototoxic sensorineural hearing loss. 

Some of the research findings

Animal model:
  • CBA/CaJ mice, 4 months of age and equal mix of males and females
  • Injury model: cyclodextrin ototoxicity by injection of 8 mg/g of body weight, injected as a single subcutaneous injection. 
  • "Cyclodextrins have been used to reduce drug volatility, mask bitterness, and improve the solubility and stability of poorly water-soluble drugs." 
  • Cyclodextrins are known to preferentially damage outer hair cells at high doses.

Damage phenotype of cyclodextrin-treated mice:

  • 1 day post-treatment, substantial loss of OHC is observed. 
  • 6 weeks after the treatment, the auditory brainstem response shows substantial hearing loss, particularly for high frequencies. 
  • Both outer and inner hair cells were lost, particularly in the higher frequency zone or towards the base of the cochlea. 
Supporting cell response to ototoxic injury (after 6+ weeks): 
  • Despite severe OHC loss, most supporting cells survived in the apical and middle turns.
  • After 6+ weeks, in the basal turn, supporting‑cell loss was substantial; however, a subset of Deiters’ cells survived and remained intact in both OHC present and absent areas. 
  • Where Deiters' cells were lost, the reticular lamina was completely absent.
  • Hensen’s cell reduction began in the middle cochlear region and exceeded the loss observed for Deiters’ and pillar cells there.
  • Where Deiters' cells are lost, Hensen’s cells (visualised using Galectin-3) participate in structural repair by re-epithelializing denuded areas of the basilar membrane. At this stage, Hensen's cells are enlarged and flatter in appearance. 
  • When the organ of Corti collapsed, Hensen’s cells contributed to forming a continuous epithelial layer over the basilar membrane. The authors suggest this is evidence of a repair phenotype. 

Supporting cells show graded, cell‑type‑ and location‑specific vulnerability after cyclodextrin ototoxicity.
Part of Fig 9B. Hensen's cells approaching the damaged organ of corti. Ding et al. 2025.

Haruna's takeaway

This is a very cool paper! I like how this research focuses on one model, but compares Deiters' cells, Hensen's cells and Piller cells more comprehensively. I have to say I have not paid much attention to Hensen's cells, except that we always see them in the back of our eyes when we are looking at the organ of Corti in cochlear tissue section or whole mount preparations. Graded responses by different supporting cell types suggest different roles they play depending on the progression of pathologies in the cochlea. The difference between different supporting cells is also very important for any future research aiming to enable regenerative therapy. 

 ------- 

This is Haruna's 68/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.