Note: Post 4878 about using other stem cells for MD in dogs
Post 6184 : Using reprogrammed SCs for MD
Stem-cell transplantation improves muscles in MD animal model, UT
Southwestern researchers report
DALLAS – Jan. 20, 2008 – Using embryonic stem cells from mice, UT
Southwestern Medical Center researchers have prompted the growth of
healthy – and more importantly, functioning – muscle cells in mice
afflicted with a human model of Duchenne muscular dystrophy.
The study represents the first time transplanted embryonic stem cells
have been shown to restore function to defective muscles in a model
of muscular dystrophy.
The researchers' newly developed technique, which involves stringent
sorting to preserve all stem cells destined to become muscle, avoids
the risk of tumor formation while improving the overall muscle
strength and coordination of the mice, the researchers found.
The mice used in the study lacked dystrophin, the same protein that
humans with the fatal wasting disease also are missing.
The study, headed by Dr. Rita Perlingeiro, assistant professor of
developmental biology and molecular biology, is available online
today and in the February issue of Nature Medicine.
"We envision eventually developing a stem-cell therapy for humans
with muscular dystrophy, if we are able to successfully combine this
approach with the technology now available to make human embryonic
stem cells from reprogrammed skin cells," Dr. Perlingeiro
said. "These cells can be transplanted into the muscle, and they
cause muscle regeneration resulting in stronger contractility.
The study represents a major step in the field, she said, because the
researchers were able to tease out exactly the cells they wanted.
"The problem had been that embryonic stem cells make everything," Dr.
Perlingeiro said. "They make a great variety of cells. The trick is
to pull out only the one type you want."
The UT Southwestern researchers focused on manipulating genes that
are active in the very early stages as embryonic stem cells start to
develop into more specialized cells. At first, they activated a gene
called Pax3, which is involved in creating muscle cells, and then
injected those cells into the animals' muscles. Those cells caused
tumors containing many different types of cells, indicating that
there were still residual undifferentiated embryonic stem cells in
the cultures at the time of implantation.
"Even if there are 10 undesirable cells, that's too many," Dr.
Perlingeiro said.
The researchers then began using fluorescent dyes to sort cells
depending on whether some surface markers were turned on while others
were turned off. By analogy, it was as if they were dealing with a
crowd of people and wanted to pull out only those with red hair,
green scarves and blue coats, while those with red hair, green
scarves and no coats would be disqualified.
The final selection of cells, containing only one type, was again
injected into the animals' hind-limb muscles. After a month, the
fluorescent dyes showed that the cells had deeply penetrated the
muscle, an indication that they were growing and reproducing as
desired, and many of the muscle fibers also contained dystrophin, the
key protein lacking in muscular dystrophy.
After three months, the mice also showed no signs of tumors.
Tests of isolated muscles showed that the treated muscles were
significantly stronger than untreated mice lacking dystrophin,
although not quite as strong as those of normal mice.
The treated mice also were tested for coordination. Again, their
performance was better than that of untreated mice, but not as good
as that of normal mice.
"The improved coordination is significant because it shows the
embryonic stem cells have benefited the animal's quality of life, not
simply caused an isolated growth with no overall improvement,
Perlingeiro said.
The researchers will next investigate whether these transplanted
cells can make "muscle stem cells," which are partially developed
cells in muscle tissue that serve as a reserve to replenish muscles.
They also are testing their implantation approach in animal models of
other types of muscular dystrophy.
###
Other UT Southwestern researchers involved in the study were lead
author Dr. Radbod Darabi, postdoctoral researcher in developmental
biology; allied health student Kimberly Gehlbach; Dr. Robert Bachoo,
assistant professor of neurology and internal medicine; Shwetha
Kamath, research assistant in developmental biology; Dr. Mitsujiro
Osawa, postdoctoral fellow in developmental biology; Dr. Kristine
Kamm, professor of physiology; and Dr. Michael Kyba, assistant
professor of developmental biology and molecular biology.
The work was supported by the Dr. Bob and Jean Smith Foundation.
Visit
http://www.utsouthw
to learn more about UT Southwestern'
neuromuscular disorders.
This news release is available on our World Wide Web home page at
www.utsouthwestern.
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mail, subscribe at www.utsouthwestern.
Dr. Rita Perlingeiro -
http://www.utsouthw
l
Public release date: 20-Jan-2008
Contact: Aline McKenzie
aline.mckenzie@
214-648-3404
UT Southwestern 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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