In an earlier column about the recent Stem Cell Symposium
held on the Promega Campus, I extolled the exciting frontier of stem cell basic
science that was on display; however, it was just as interesting to catch up with
local stem cell researchers who attended the Symposium. I caught a glimpse of the current status of
stem cell science in the Madison area.
Other health benefits
of embryonic stem cells
For instance, I ran into Tim Kamp, an MD in the UW-Madison
Department of Cardiology who, along with Professor Jamie Thomson, recently
developed a reliable way to derive human heart cells from embryonic stem cells
(ESCs).
About four years ago I first met Kamp in his UW-Madison
office to learn about his research. At
that time, researchers knew that when given the chance, human ESCs haphazardly differentiate
in tissue culture into all the different tissue types and Kamp, using a microscope,
had been able to find among the clutter of different cells a few well developed
heart cells that actually were beating! You can see a short video clip of one of the beating heart cells here.
Using a steady-handed robot, Kamp inserted a very fine probe
into a beating heart cell and measured its depolarization or the exchange of
ions across its membrane, which constitutes the electric current that causes
heart muscle to beat. With this, he
recorded an “EKG” on a single human heart cell that changed as expected when he
added to the culture, a drug often given to heart patients.
Currently, animal models are the best way to measure
pharmacological effects of drugs on the heart—an important but insufficient
model since 30% of drug failures are due to cardiotoxicity. Clearly, we need ways to test drugs on human
heart cells, but until the advent of ESCs, there was no reliable way to obtain
and grow them in the lab. Now, being
able to derive functional heart muscle cells from ESCs provides a important option
for testing drugs on real human heart tissue, thereby improving the safety and
efficacy of new drugs. At least this was
Kamp’s goal four years ago when I talked with him in his office.
Things seem to be progressing well. A couple of years ago, Kamp and his
co-workers launched the local biotechnology company, Cellular Dynamics
International, in order to bring this technology to fruition. In early March, Roche Palo Alto reached an
agreement with CDI to begin using their ESC-derived heart cells for testing the
cardiotoxicity of candidate drug compounds.
Using ESCs to derive fully functional mature cell types for
testing potential drugs and toxins directly on human tissues is an
under-appreciated and poorly communicated application for ESCs, but one that
will soon be widely employed in the pharmaceutical industry. Thus, human ESCs will likely play an
important role in human health, even if they are never used to directly treat
human disease.
Kamp indicated that similar screening methods are being developed
for other tissue cell types derived from human ESCs.
Treating neurological
diseases
A few years ago, I attended a seminar by UW-Madison
neuroscientist, Clive Svendson, who showed a video clip of patients with
Parkinson’s disease before and after treatment with a nerve cell factor known
as GDNF. The result was a dramatic slowing
of disease progression in treated patients.
As encouraging as this therapy was, it remains highly
experimental since GDNF cannot cross the blood-brain barrier and must be
delivered by cannula—a thin tube inserted deep into the brain area affected by
Parkinson’s disease—not an attractive long term option.
Furthermore, GDNF therapy only retards the progressive loss
of dopamine producing neurons that is characteristic of Parkinson’s disease; it
does not reverse the process. Therefore,
this will not likely benefit patients with advanced disease who have lost too
many of these critical cells. This is
where the hope of stem cell therapy merges with the other great therapeutic
hope—gene therapy.
For instance, ESCs alone are not likely to be much of a
benefit for patients with Parkinson’s, because stem cell-derived dopamine-producing
neurons transplanted in the brains of Parkinsonian patients likely will suffer
the same fatal fortune as their endogenous predecessors. But, combine stem cell regeneration of the
neurons with in situ production of
GDNF via gene therapy technology and you just may be able to sustain
dopamine-producing cells for the long term. Or so the hope goes.
A similar idea is being tested in Svendsen’s lab for
treating amyotrophic lateral sclerosis; also know as ALS or Lou Gehrig’s
disease. Like Parkinson’s, ALS is
caused by the progressive and irreversible loss of certain critical neural
cells in the brain. Svendsen’s lab has developed
rat and primate models of ALS and using human fetal-derived neural stem cells,
in conjunction with gene transfer technology, have successfully implanted fully
functional, GDNF producing neurons in brains of these ALS animals. The results are very encouraging at this
point--they see long-term survival of the transplanted cells and sustained
production of GDNF, and these correlate with resolution of symptoms.
This is not the first example using ESCs to successfully
treat human diseases in animal models, but ESCs have not yet made it into the
clinic. Human trials will likely begin in
the next year or two and the FDA is now considering how to best monitor them
for safety and efficacy--not a trivial undertaking, but, stay tuned.
Moving stem cell science
along
At the symposium I also had the chance to connect with Eric
Forsberg, the recently appointed Director of WiCell. This is the non-profit spin-off from the
Wisconsin Alumni Research Foundation (WARF) that provides support for stem cell
researchers at UW-Madison.
According to Forsberg, WiCell, not only maintains the
National Stem Cell Bank, it also engages in outreach activities and provides
core services for stem cell researchers that are not found elsewhere on the
UW-Madison campus. Forsberg pointed out
that WiCell is also happy to provide such support and training for private stem
cell companies in order to foster the development of cell-based medicine in Wisconsin..
Forsberg hopes to soon partner with the Waissma Center
on the UW-Madison campus to begin a trial run to grow clinical-scale batches of
ESCs under the cGMP conditions that are required in order to use the cells to
treat patients. The Waissman Center has the cGMP facilities to produce biological materials for clinical use.
This will be a proof-of-principle endeavor designed to show
that ESCs can be produced in clinically relevant quantities while maintaining
their state of differentiation. Unforeseen problems, the bane of any biotechnology research, will be
identified and resolved during this trial run so they will be ready when the
time comes to quickly move ESCs into clinical trials.
We rapidly approach the day when ESCs will be used in
experimental therapies of human diseases. Probably the first trials will use blood or bone marrow products derived
from ESCs as a donor source for marrow transplantation or red cell transfusion.
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© 2008 Steven S. Clark,
PhD. Disclaimer: The authors used their
best efforts in collecting and preparing the information published herein.
However, Steven S. Clark, nor other authors, do not assume, and hereby
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Articles contained herein,
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