Scientists at UCLA reprogram human skin cells into embryonic stem
cells
By Kim Irwin| 2/11/2008 2:00:00 PM
UCLA stem cell scientists have reprogrammed human skin cells into
cells with the same unlimited properties as embryonic stem cells,
without using embryos or eggs.
Led by scientists Kathrin Plath and William Lowry, UCLA researchers
used genetic alteration to turn back the clock on human skin cells
and create cells that are nearly identical to human embryonic stem
cells, which have the ability to become every cell type found in the
human body. Four regulator genes were used to create the cells, which
are called induced pluripotent stem cells, or iPS cells.
The UCLA study confirms the work of researchers Shinya Yamanaka at
Kyoto University and James Thomson at the University of Wisconsin,
first reported in late November 2007. The UCLA research appears today
in an early online edition of the journal Proceedings of the National
Academy of the Sciences.
The implications for disease treatment could be significant.
Reprogramming adult stem cells into embryonic stem cells could
generate a potentially limitless source of immune-compatible cells
for tissue engineering and transplantation medicine. A patient's skin
cells, for example, could be reprogrammed into embryonic stem cells,
and those stem cells could be prodded into becoming various cells
types beta islet cells to treat diabetes, hematopoetic cells to
create a new blood supply for a leukemia patient or motor neuron
cells to treat Parkinson's disease.
"Our reprogrammed human skin cells were virtually indistinguishable
from human embryonic stem cells," said lead author Plath, an
assistant professor of biological chemistry and a researcher with
UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem
Cell Research. "Our findings are an important step towards
manipulating differentiated human cells to generate an unlimited
supply of patient-specific pluripotent stem cells. We are very
excited about the potential implications.
The UCLA work was completed at about the same time the Yamanaka and
Thomson reports were published. Taken together, the studies
demonstrate that human iPS cells can be easily created by different
laboratories and are likely to mark a milestone in stem cell-based
regenerative medicine, Plath said.
These new techniques to develop stem cells could potentially replace
a controversial cell-reprogramming method known as somatic cell
nuclear transfer (SCNT), which is sometimes referred to as
therapeutic cloning. To date, therapeutic cloning has not been
successful in humans. However, top stem cell scientists worldwide
stress that further research comparing these reprogrammed iPS cells
with stem cells derived from embryos considered the gold standard
is necessary. Additionally, many technical problems, such as the use
of viruses to deliver the four genes for reprogramming, need to be
overcome to produce safe iPS cells that can be used in the clinic.
"Reprogramming normal human cells into cells with identical
properties to those in embryonic stem cells without SCNT may have
important therapeutic ramifications and provide us with another
valuable method to develop human stem cell lines," said first author
Lowry, an assistant professor of molecular, cell and developmental
biology and a Broad Stem Cell Center researcher. "It is important to
remember that our research does not eliminate the need for embryo-
based human embryonic stem cell research but rather provides another
avenue of worthwhile investigation.
The four genes used in combination to reprogram the skin cells
regulate expression of downstream genes and either activate or
silence their expression. The reprogrammed cells were not just
functionally identical to human embryonic stem cells they also had
an identical biological structure, expressed the same genes and could
be coaxed into giving rise to the same types of cells.
The UCLA research team included four young scientists recruited to
UCLA's new stem cell center following the passage of California's
Proposition 71 in 2004, which created $3 billion in funding for
embryonic stem cell research. The scientists were drawn to UCLA in
part because of California's stem cell research-friendly atmosphere
and the funding opportunities created by the initiative. In addition
to Plath and Lowry, the team included Amander Clarke, assistant
professor of molecular, cell and developmental biology, and April
Pyle, assistant professor of microbiology, immunology and molecular
genetics.
The creation of the human iPS cells is an extension of Plath's work
on mouse stem cell reprogramming. Plath headed one of three research
teams that were able to successfully reprogram mouse skin cells into
mouse embryonic stem cells. That work appeared in the inaugural June
2007 issue of the journal Cell Stem Cell.
UCLA's stem cell center was launched in 2005 with a UCLA commitment
of $20 million over five years. A $20 million gift from the Eli and
Edythe Broad Foundation in 2007 resulted in the renaming of the
center.
The Eli and Edythe Broad Center for Regenerative Medicine and Stem
Cell Research at UCLA, with more than 150 members, is committed to a
multidisciplinary, integrated collaboration of scientific, academic
and medical disciplines for the purpose of understanding adult and
human embryonic stem cells. The institute supports innovation,
excellence and the highest ethical standards focused on stem cell
research with the intent of facilitating basic scientific inquiry
directed towards future clinical applications to treat disease. The
center is a collaboration of the David Geffen School of Medicine at
UCLA, UCLA's Jonsson Comprehensive Cancer Center, the UCLA Henry
Samueli School of Engineering and Applied Science, and the UCLA
College of Letters and Science. To learn more about the center, visit
www.stemcell.
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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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1 comment:
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