UCLA stem cell researchers create heart and blood cells from
reprogrammed skin cells
Discovery may lead to new treatments
Stem cell researchers at UCLA were able to grow functioning cardiac
cells using mouse skin cells that had been reprogrammed into cells
with the same unlimited properties as embryonic stem cells.
The finding is the first to show that induced pluripotent stem cells
or iPS cells, which don't involve the use of embryos or eggs, can be
differentiated into the three types of cardiovascular cells needed to
repair the heart and blood vessels.
The discovery could one day lead to clinical trials of new treatments
for people who suffer heart attacks, have atherosclerosis or are in
heart failure, said Dr. Robb MacLellan, a researcher at the Eli and
Edythe Broad Center of Regenerative Medicine and Stem Cell Research
and senior author of the study. Researchers also were able to
differentiate the iPS cells into several types of blood cells, which
may one day aid in treating blood diseases and in bone marrow
transplantation.
"I believe iPS cells address many of the shortcomings of human
embryonic stem cells and are the future of regenerative medicine,"
said MacLellan, an associate professor of cardiology and
physiology. "I'm hoping that these scientific findings are the first
step towards one day developing new therapies that I can offer my
patients. There are still many limitations with using iPS cells in
clinical studies that we must overcome, but there are scientists in
labs across the country working to address these issues right now."
The study, which brought together stem cell and cardiology
researchers at UCLA, appears online May 1, 2008 in the journal Stem
Cells. The article can be accessed at
www.stemcells.
Last June, UCLA stem cell researchers were among several scientific
teams that were the first to reprogram mouse skin cells into cells
resembling embryonic stem cells, which have the ability to become
every cell type found in the body. MacLellan and his team used UCLA's
iPS cells in their study.
Although iPS cells are believed to be very similar to embryonic stem
cells, further study needs to be done to confirm their
differentiation potential. MacLellan's study proved that iPS cells
can be induced into becoming cardiovascular cells, an important step
in the confirmation process.
"Theoretically, iPS cells are able to differentiate into 220
different cells types," said Dr. Miodrag Stojkovic, co-editor of Stem
Cells. "For the first time, scientists from UCLA were able to induce
the differentiation of mouse iPS cells into functional heart cells."
In MacLellan's study, the iPS cells were cultured on a protein matrix
known to direct embryonic stem cells into differentiating into
cardiovascular progenitor cells, immature heart cells that can give
rise to mature cardiac cells that perform different functions. The
progenitor cells were then isolated from the other iPS cells that did
not differentiate using a protein marker called KDR, a growth factor
receptor expressed on the surface of the progenitor cells.
Once isolated, the cardiovascular progenitor cells were coaxed into
becoming cardiomyoctyes, or mature heart muscle cells that control
heartbeat, endothelial cells, which form rudimentary blood vessels,
and vascular smooth muscle cells, the specialized cells that line
blood vessel walls. Once mature, the cardiomyocytes beat in the Petri
dish.
Studies are under way now at UCLA to determine if human iPS cells
behave the same way as the mouse cells behave. If they do, the time
may come when a person could use their own skin cells to create
individualized iPS cell lines to provide cells for cardiac repair and
regeneration, MacLellan said.
It is vital to be able to grow and isolate progenitor, or partially
differentiated, cells that can create the three types of cardiac
cells for potential clinical use. When embryonic stem cells are
injected directly into the heart in animal models, they create tumors
because the cells differentiate not only into cardiac cells but into
other cells found in the human body as well. Likewise, using
embryonic stem cells garnered from other sources than the patient
could result in rejection of the injected cells.
The use of iPS cells may solve those problems. If the iPS cells come
from the patient, rejection should not be an issue. Additionally, the
use of cells that are already partially transformed into specific
cardiac cell types may prevent tumor growth. The use of iPS cells
also sidesteps the controversy some associate with deriving
pluripotent stem cells from embryos or eggs, MacLellan said.
"Our hope is that, based on this work in mice, we can show that
similar cardiovascular progenitor cells can be found in human iPS
cells and, using a similar strategy, that we can isolate the
progenitor cells and differentiate them into the cells types found in
the human heart," MacLellan said.
###
The 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. With more than 150 members, the Eli and Edythe Broad Center
for Regenerative Medicine and Stem Cell Research is committed to a
multi-disciplinary, 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,
UCLA's Jonsson Cancer Center, the Henry Samueli School of Engineering
and Applied Science and the UCLA College of Letters and Science. To
learn more about the center, visit our web site at
http://www.stemcell
Public release date: 30-Apr-2008
Contact: Kim Irwin
kirwin@mednet.
310-206-2805
University of California - Los Angeles
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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