The Origins of Regenerated Hair Cells
by Cheryl Heppner
Editor: The 2005 SHHH Convention's 12th Annual Research Symposium was
on the Origins of Regenerated Hair Cells. Those who are following this
research know that scientists are making substantial progress towards
the day when they'll be able to regrow hair cells in humans; they also
know that day is stills a ways off.
Here's Cheryl's report on this very interesting symposium. If you'd
like to share this article, please be sure to credit NVRC. (See credit
at the end of the article.)
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Hair Cell Regeneration by Dr. Jeffrey T. Corwin
Applications for Stem Cells in Restoring Hearing Loss
by
Dr. Stefan Heller
Identifying Hair Cell Precursors by Dr. Neil Segil
Development of the Cochlear Sensory
Epithelium by
Dr. Matthew W. Kelley
Department of Neuroscience, University of Virginia
- The number of hair cells in both the inner and outer ear declines
as we age.
- Early research on fruit flies led to further research. In the 1970s
Dr. Corwin was in the Central Pacific -- Enewetak Atoll -- studying how
sharks could hear and locate sounds. In 1974 he found that a juvenile
shark had 20,000 hair cells but a mature adult had 240,000 hair cells.
In humans, nerve deafness is permanent and we don't regenerate hair
cells.
- Sharks, bony fish and amphibians get new hair cells from cells that
are regenerated when supporting cells divide.
- Doug Cotanche at the University of Hawaii did key research on hair
cell regeneration. He was studying birds for technical reasons, and it
was accidental that he exposed birds to loud sounds, then got them to
sit for 10 days. He found that one preserved its cells immediately, and
that stimulated interest. The newly regenerated hair and support cells
contained new DNA.
- A laser was used to focus inside a hair cell nucleus, and a pulse
was given to shoot and kill them. Time-lapse photography showed that
support cells nearby divided and reproduced.
- In non-mammals, hair cell regeneration goes in stages. The support
cells lose their specialty, divide and become two cells. The offspring
can specialize as either a supporting cell or hair cell. The default
fate is to become a hair cell unless the cell is inhibited from adapting
that fate. Replacement hair cells form synapses and restore hearing and
balance function.
- One graduate student liked to tell others that if they were at a
rock concert, and stood next to a speaker for a certain amount of time
with a chicken, the chicken's hair cells would grow back in 10 days but
human hearing loss would be permanent. We're trying to become more like
chickens.
- Can mammals regenerate hair cells? Tissue from a 52-year-old
patient that would normally be discarded was brought back to the lab.
They wanted to see if it had the machinery to regenerate. The result was
encouraging. Replicated DNA showed new cells could form in hair cell
organs in mature human ears.
- It showed the machinery can occur in older mammals, with hundreds
of cells in a human. But in a bird you would have seen tens of thousands
of hair cells.
- The question then becomes: Can we enhance the occurrence of cell
divisions in mammal ears through supporting cells and wake up the
regeneration machinery in the ear? Or as some scientists like to say,
"a way to step on the gas pedal."
- In tissue culture we can now strongly enhance the proliferation of
supporting cells in the mammalian ear with two drugs --forskolin and a
biotech drug rhGGF2.
- So what are the limits of regeneration? One is the age of the
animal. In examining tissue of a newborn, during the first couple of
weeks of life, supporting cells were found to be becoming quiescent.
- Microsurgical cuts were made, and these excision wounds healed
rapidly in ears from embryonic mammals.
- Persistent hearing and balance losses are all too common and result
in the loss of one type of cell. That just one type of cell is
responsible is very important to pharmaceutical and biotech companies.
Whether it is a bird or fish, all lose hearing for the same reason.
- Animal models for damage that results in hearing and balance loss
are truly representative of humans.
- Supporting cells are the source of the cells that specialize as
hair replacement cells.
- What is reasonable to expect from research in regeneration? We
could get a major breakthrough at any time. Often breakthroughs are just
an accident when scientists are looking for something else. Research is
moving faster and faster. Most people in research are optimists.
- Steps needed for hair cell regeneration:
1. Induce cell production
2. Suspend quiescence
3. Induce differentiation (specialization of new cells as replacement
hair cells)
Q: Why did mammals lose the ability to regenerate hair cells?
A: There's no clear reason why it would be an advantage to lose hair
cells. What's unique about our hair cells is that they have a
single-file line, very structured. At no place else in the body do cells
line up in such order. We don't know any reason why evolution would have
caused that.
Q: We don't have a Nancy Reagan to support this research, and the
deaf community opposes it. What should be done?
A: It's completely different for people born deaf than those who develop
hearing and lose it. That point needs to get across. We now have only
about 1/3 of the funding needed for this level of research and the
proposed federal budget cuts this amount. Only about 2/3 of the work
underway will continue to be funded if that amount is not increased.
