The Origins of Regenerated Hair Cells
by Cheryl Heppner
Dr. Stefan Heller
Massachusetts Eye and Ear Infirmary
Harvard Medical School
- You don't hear with the hair cells, you hear with the brain. For
that reason it would be much better to have a biological cure than a
cochlear implant.
- Loss of hearing comes in two phases when you age. First the number
of outer cells, which make the vibration in your ear, gets smaller. You
can still hear, but you need higher sound levels and stimulation. Next
the inner cells are affected. Those are more complicated. When you lose
those, you can't hear at all. But you can still use a cochlear implant
to stimulate the auditory nerve.
- The possible treatments for regeneration are:
1. Drugs, but these are very labor-intensive and use a lot of animals
2. Viral, introducing Atoh1 with gene therapy, but this is far away from
any clinical application at the moment
3. Stem cell, grafting progenitor cells with human cells to speed things
up
- Is it possible to regenerate hair cells from stem cells? There are
two populations of stem cells you can use -- embryonic and adult. The
embryonic cells grow on top of others.
- Some mouse cells were taken and transplanted to the ear in the
cochlea of a chicken embryo. From this experiment, it was learned that
it's possible to generate from embryonic stem cells a population of
progenitor cells to transplant in an embryonic cochlea.
- Now attempts are needed to try in utero stem cell therapy,
injecting stem cells. There are many roadblocks ahead and many more
steps before the science is ready for this to be done in humans.
- Drug screening for compounds that induce hearing cell regeneration
in a test tube are another approach. Researchers would like to use human
embryonic cells, but will have to adapt all they have learned from mouse
cells.
- Are there possible alternatives for embryonic stem cells? Adult
stem cells from the nervous system ("neural stem cells")
didn't work well. Others have been tried -- bone marrow, skin, etc.
- Can we find inner ear stem cells? Research found that there are
stem cells in the balance epithelia and cochlea. But the research also
discovered that there is variation in different areas. In the Organ of
Corti, cells seemed to die out fast. Vestibular system cells remained
much longer.
- The stem cells could be maintained in a lab, but it was a long and
arduous process to build, maintain and increase them. Expansion and
long-term storage isn't optional.
- Stem cells have been isolated from the ear. In the past year,
they've gone from isolating 15 cells from one to 250 cells.
- Cultures can be done of human adult hair cells so they won't have
to do human testing. This looks promising.
- Embryonic, inner ear and other stem cells all need cell delivery
into the inner ear, and safety studies must be addressed.
- Spiral ganglion cells (neurons) have an important role. If you have
these cells, you can hear with a cochlear implant. If you don't, you
cannot hear with a cochlear implant. These cells get signals from the
hair cells to the brain. In auditory neuropathy, the hair cells work but
people can't hear, and this is most likely due to the absence of spiral
ganglion cells.
- It is more complicated to replace hair cells, but replacing neurons
should be easier. Neural progenitors were grafted into a de-afferented
gerbil cochlea. This wasn't expected to work so well as it did. It's now
being studied in a second and third batch of animals.
- Inner ear cell regeneration therapy has been and will continue to
be a long road.
- Both gene therapy and progenitor cell transplanting are in very
early experimental stages.
- Stem cell-based approaches have no alternative for human embryonic
stem cells. They are the only appropriate cell group.
- There are different flavors of hair cells. Not only are there inner
and outer ear cells, but the ear has certain frequencies.
- If gene therapy is used to regenerate cells, it would not pass to
offspring.
- Japanese researchers are testing with grafting stem cells at
different locations to see where they show up.
- Researchers have used every growth factor they could get their
hands on to try to restimulate hair cells. This is probably best. No
drug has been discovered, but a gene has.
- Dr. Heller is concerned not just about continued funding but also
about continually attracting people to the field.
Q: Drugs are being used to stimulate cell growth; have you thought
about nutrition?
A: Yes, that is done all the time. A very nutritious growing medium is
used.
Q: Where is most of the research being done?
A: About 3/4 of the inner ear regeneration is being done in the US. A
couple of groups are also working in Europe. Luckily there is a good
exchange and collaboration among researchers, not a group that is nasty
to each other.
