Researchers at the Institute
for Stem Cell Biology and Medicine at UCLA were able to take normal tissue
cells and reprogram them into cells with the same unlimited properties as
embryonic stem cells, the cells that are able to give rise to every cell type found
in the body.
The work, done in mouse
models, appears in the inaugural June 7 issue of the journal Cell Stem Cell,
published by Cell Press. UCLA researchers, working closely with stem cell
scientists at Harvard
University, took mouse
fibroblasts, cells that develop into connective tissue, and added four
transcription factors that bind to special sites on the DNA. Using this
process, they were able to turn the fibroblasts into pluripotent
cells that, in every aspect tested, were identical to embryonic stem cells.
The implications for disease
treatment could be staggering. Reprogramming adult stem cells into embryonic
stem cells could generate a potentially limitless source of immune-compatible
cells for tissue engineering and transplantation medicine. If the work can be
replicated in human cells, it may mean that a patient's skin cells, for
example, could be reprogrammed to become embryonic stem cells. Those embryonic
stem cells could then 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.
"If we can recreate this in
human cells, it has significant implications for regenerative therapies," said study
co-lead author Kathrin Plath, UCLA assistant professor of biological chemistry
and a researcher with the Institute for Stem Cell Biology and Medicine at UCLA
(ISCBM). "Our reprogrammed cells were virtually indistinguishable from
embryonic stem cells. We could find no evidence that they were different in any
way. We were rather surprised at how well this reprogramming worked."
The finding also is
significant in that this new technique could potentially replace a
controversial method used to reprogram cells — somatic cell nuclear transfer
(SCNT), sometimes
referred to "therapeutic cloning." To date, SCNT has not been done successfully
in human cells.
"If we can successfully reprogram a normal human cell into a cell with
almost identical properties to those in embryonic stem cells without SCNT, it
may have important therapeutic ramifications and provide us with another method
to develop human stem cell lines," said Dr. Owen Witte, ISCBM director and a
Howard Hughes Medical Institute investigator. "Up until now, it's been unclear
whether a cell could be reprogrammed back into an embryonic stem cell state
without the use of SCNT, so that makes this a very important finding."
Studies published previously had shown that the four transcription factors
that regulate expression of downstream genes and either activate or silence
their expression could reprogram cells into cells with some pluripotent
properties. But they differed from embryonic stem cells in that they could not
differentiate into every cell type or support development of adult tissues.
"They had very limited developmental potential," Plath said. "We took a
different approach, carefully selecting from our pool of cells the reprogrammed
cells that highly expressed two genes we know are essential in embryonic stem
cells."
Selecting cells that highly expressed the genes Oct4 and Nanog, which are essential to giving embryonic stem cells
their unique characteristics, resulted in reprogrammed cells with much more
powerful pluripotency, Plath said.
The reprogrammed cells were not just functionally identical to embryonic
stem cells. They also had identical biological structure. In a cell nucleus, DNA — an organism's unique map or
instructions — wraps around histones, which serve as
a kind of scaffolding for compaction of the long DNA molecule. Histones don't merely package DNA. Chemical tags on histones determine which genes are expressed or shut off in
the DNA. In the reprogrammed cells, the location of the chemical tags along the
DNA chromosomes were identical to those found in embryonic stem cells and, just
as importantly, dramatically different from those in the fibroblasts before
reprogramming. The structure of the reprogrammed cells — down to the very small
chemical tags that dictate gene expression — is highly similar to that of
embryonic stem cells.
Plath and her colleagues are working now to recreate the cell reprogramming
in human cells. It could take years to determine if the same results can be
achieved.
About the Institute for Stem Cell Biology and Medicine
at UCLA
The Institute for Stem Cell
Biology and Medicine was launched in 2005 with a UCLA commitment of $20 million
over five years. With more than 150 members, the ISCBM is committed to a
multidisciplinary, integrated collaboration between 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 institute is a collaboration of the David Geffen School of
Medicine at UCLA, UCLA's Jonsson 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
Institute for Stem Cell Biology and Medicine at UCLA, visit the institute's Web
site at www.stemcell.ucla.edu.
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