Harvard-Columbia team creates neurons from ALS patient's skin cells
New key to understanding and treating ALS, and a step toward
personalized regenerative medicine
NEW YORK – Harvard and Columbia scientists have for the first time
used a new technique to transform an ALS (amyotrophic lateral
sclerosis, or Lou Gehrig's disease) patient's skin cells into motor
neurons, a process that may be used in the future to create tailor-
made cells to treat the debilitating disease. The research – led by
Kevin Eggan, Ph.D. of the Harvard Stem Cell Institute – will be
published July 31 in the online version of the journal Science.
This is the first time that skin cells from a chronically-
have been reprogrammed into a stem cell-like state, and then coaxed
into the specific cell types that would be needed to understand and
treat the disease.
Though cell replacement therapies are probably still years away, the
new cells will solve a problem that has hindered ALS research for
years: the inability to study a patient's motor neurons in the
laboratory.
ALS is caused by the degeneration and death of motor neurons, the
nerve cells which convey nerve impulses from the spinal cord to each
of the body's muscles. The death of motor neurons leads to paralysis
of these muscles, including those involved in swallowing and
breathing, and ultimately leads to death of the patient. The disease
affects about 30,000 people in the United States.
"Up until now, it's been impossible to get access to the neurons
affected by ALS and, although everyone was excited by the potential
of the new technology, it was uncertain that we would be able to
obtain them from patients' skin cells," says co-author Chris
Henderson, Ph.D., professor of pathology, neurology and neuroscience,
co-director of the Center for Motor Neuron Biology and Disease at
Columbia, and senior scientific advisor of the Project A.L.S./
Jenifer Estess Laboratory for Stem Cell Research. "Our paper now
shows that we can generate hundreds of millions of motor neurons that
are genetically identical to a patient's own neurons. This will be an
immense help as we try to uncover the mechanisms behind this disease
and screen for drugs that can prolong life."
The motor neurons were created using a new technique that reprograms
human adult skin cells into cells that resemble embryonic stem (ES)
cells. The technique used to make these cells – called induced
pluripotent stem (iPS) cells – was a major advance in the field that
was first reported last November by researchers in Japan and
Wisconsin. Those studies used skin cells from healthy adults, but it
remained unknown whether iPS cells could be created with cells from
chronically-
Columbia-Harvard team, in this paper, showed this was possible using
an ALS patient's skin cells.
Columbia clinician-researche
Irving Assistant Professor of Pediatrics in Medicine, and Hiroshi
Mitsumoto, M.D., D.Sc., the Wesley J. Howe Professor of Neurology at
Columbia, obtained skin cells from an 82-year-old ALS patient. In the
Project A.L.S. laboratory, Columbia researchers Dr. Henderson and
Hynek Wichterle, Ph.D., assistant professor of pathology, and
colleagues cultured the cells and contributed expertise needed for
identifying iPS cell-derived motor neurons. Finally, Harvard
researchers, led by Kevin Eggan of the Harvard Stem Cell Institute,
successfully used the new technique to reprogram the skin cells into
iPS cells and differentiate them into motor neurons.
Scientists had originally hoped to create neurons and other adult
cells using "therapeutic cloning," in which DNA from a patient is
inserted into a donated egg to create embryonic stem cells. That
technique, however, has still not been successful in humans, and is
also hindered by a shortage of donated eggs.
If the iPS technique holds its promise in producing neurons and other
cells for research, it will probably replace the "therapeutic
cloning" approach, Dr. Henderson says, but there are still lots of
questions about the iPS-derived neurons.
"We don't know yet how similar they are to the motor neurons in ALS
patients," he says. "While the cells exhibit many properties that are
typical of motor neurons, we don't yet know whether they will be
prone to degeneration that will allow us to mimic the disease in the
culture dish and therefore to screen potential drugs."
Researchers at Columbia and Harvard are already collaborating to
investigate the cells with the ultimate goal of determining how they
differ from a healthy person's motor neurons.
"Project A.L.S. has always maintained that collaboration between
scientists is the answer to understanding and treating this disease,"
Valerie Estess, founder and research director, Project A.L.S. "We are
thrilled to have catalyzed the Harvard-Columbia collaboration that
led to this discovery."
"Therapeutic use of the cells is probably a long way off," Dr.
Henderson says. "Right now there are safety issues with iPS cells,
including a risk of cancer. We also don't know how to reintroduce
cells into a sick adult in a way that will be beneficial. All these
hurdles need to be overcome first before we can think about using the
cells to treat disease, but we can start immediately to evaluate them
as a tool for drug discovery."
###
The Columbia and Harvard researchers were supported by the Harvard
Stem Cell Institute, Project A.L.S., the SMA Foundation, MDA Wings
Over Wall Street, the Claire and Leonard Tow Charitable Foundation,
the Spina, Drago and Bowen Families, Ride for Life and the New York
Stem Cell Foundation.
*** Related Teleconference: A teleconference related to the
forthcoming Science paper, "Induced pluripotent stem cells generated
from patients with ALS can be differentiated into motor neurons," by
Dr. Eggan and colleagues is planned for 12 noon, U.S. Eastern Time,
Wednesday, 30 July. All information released during the
teleconference will remain under embargo until 2:00 p.m. U.S. ET
Thursday, July 31. NB: The teleconference will be recorded and posted
on the web, and by calling in you are consenting to be recorded. Call
in numbers are as follows: From the United States: 1-800-311-9410.
From outside the United States: 1334-232-7224. The password
is "stemcell"
The final roster of speakers has yet to be determined, but will at a
minimum include Kevin Eggan of the Harvard Stem Cell Institute, and
Chris Henderson of Columbia University. The embargoed press briefing
is being organized by the Harvard Stem Cell Institute and Columbia
University, in cooperation with Science ***
Columbia University Medical Center is home to the Eleanor and Lou
Gehrig MDA/ALS Center, which cares for over 300 ALS patients each
year, the Center for Motor Neuron Biology and Disease, with more than
40 scientists working to uncover the cause of ALS and other motor
neuron diseases, and the Project A.L.S./Jenifer Estess/Laboratory for
Stem Cell Research. In recent years, CUMC scientists have discovered
that motor neurons may be degenerating in ALS in response to a toxin
released by neighboring cells; developed ways to turn embryonic stem
cells into motor neurons; and uncovered how motor neurons mature and
find their way to their target muscles (most recently in a paper
published this week in Cell by Thomas Jessell, Ph.D., the Claire Tow
Professor of Neuroscience, Biochemistry & Molecular Biophysics and
Investigator, Howard Hughes Medical Institute). This progress and the
present article moves Columbia scientists and their colleagues closer
to their long-term goal of finding a cure for this dreaded disease.
Columbia University investigators in the Naomi Berrie Diabetes Center
are also collaborating with Dr. Eggan and others in the Harvard Stem
Cell Institute on similar experiments on skin cells taken from
patients with diabetes. In January 2008, Columbia University received
$2.5 million from New York State's Empire State Stem Cell Board, an
agency created by the state legislature to support stem cell
research.
Columbia University Medical Center provides international leadership
in basic, pre-clinical and clinical research, in medical and health
sciences education, and in patient care. The medical center trains
future leaders and includes the dedicated work of many physicians,
scientists, public health professionals, dentists, and nurses at the
College of Physicians & Surgeons, the Mailman School of Public
Health, the College of Dental Medicine, the School of Nursing, the
biomedical departments of the Graduate School of Arts and Sciences,
and allied research centers and institutions. Established in 1767,
Columbia's College of Physicians & Surgeons was the first institution
in the country to grant the M.D. degree and is among the most
selective medical schools in the country. Columbia University Medical
Center is home to the largest medical research enterprise in New York
City and state, and one of the largest in the United States. For more
information, please visit www.cumc.columbia.
Public release date: 31-Jul-2008
Contact: Alex Lyda
mal2133@columbia.
212-305-0820
Columbia University Medical Center
http://www.eurekale
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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