In a remarkable study, a research team from the University of Sheffield in England has improved the hearing of deaf animals by using embryonic stem cells. This result should certainly give new hope to those who suffer from hearing disorders.
In this study, an uncommon for of deafness that affects perhaps less than 1% and no more than 15% of all hearing-impaired patients, was treated. Even though this treatment would not benefit all cases of hearing impairment, the strategy developed in this study could be expanded to apply to other cases of deafness. Since these results are strictly pre-clinical in nature, it will be years before human patients might benefit from them.
This work used gerbils are a model system and the results were reported in the international journal Nature. The research team was led by Dr. Marcelo Rivolta and the scientists in his laboratory.
To induce deafness in the gerbils, the scientists ablated (killed off) those nerve cells that transmit auditory information from the ear to the brain. The nerve cells are called “spiral ganglia neurons” or SGNs, and if a patient suffers damage to the SGNs, they will not be able to receive a cochlear implant to restore their hearing. Therefore, this experiment attempted to replace these SGN cells in order the restore hearing.
Rivolta’s group used human embryonic stem cell (hESC) lines H7, H14, and Shef1 and treated them with two growth factors, FGF3 and FGF10. The combination of these two growth factors induced the expression of a whole host of genes normally found in SGN cells (for example, Pax8 & Sox2). These treatments converted the hESCs into otic neural progenitors (ONPs).
In order to destroy the SGN cells in the ears of gerbils, Rivolta and others used a drug called ouabain. This drug, when injected into the inner ear, will destroy the SGN cells and make the animals completely deaf. In the next experiment, Rivolta et al. transplanted the immature nerve cells into the ears of 18 gerbils. One ear received the transplantation, while the other ear was kept as is as a control.
10 weeks later, they used electrophysiology tests to measure the response of the brain to sound. Of the 18 gerbils transplanted with the hESC-derived ONPs, the animals had recovered their hearing by an average of 46%. The recovery differed from animal to animal, but it ranged from modest recovery to almost complete in others.
All animal subjects were kept on anti-rejection medications to prevent rejecting the implanted human cells. In order to prevent tissue rejection in human patients, either induced pluripotent stem cells should be used, or hESCs that match the tissue types in the patient.
Rivolta’s team is also in the process of making immature versions of a second kind of inner-ear cell, that is, the “hair cell” that detects the auditory vibrations in the cochlea. The induction of ONPs from hESCs tends to produce two types cells: ONPs and otic epithelial progenitors (OEPs), which are the precursors of cochlear “hair cells.” Since damage to hair cells is far more common in cases of hearing loss, implantation of such cells should be able to treat far more cases of hearing loss. Unfortunately, this has not yet been tested in animals, according to Rivolta.
Yehoash Raphael of the University of Michigan, who didn’t participate in the work, said it’s possible the stem cell transplants worked by stimulating the gerbils’ own few remaining nerve cells, rather than creating new ones. But either way, “this is a big step forward in use of stem cells for treating deafness.”
Likewise, Lawrence Lustig of the University of California, San Francisco, said, “It’s a dynamite study (and) a significant leap forward.”