Reprogrammed human adult stem cells rescue diseased muscle in mice
Scientists report that adult stem cells isolated from humans with
muscular dystrophy can be genetically corrected and used to induce
functional improvement when transplanted into a mouse model of the
disease. The research, published by Cell Press in the December issue
of Cell Stem Cell, represents a significant advance toward the future
development of a gene therapy that uses a patient's own cells to
treat this devastating muscle-wasting disease.
Duchenne muscular dystrophy (DMD) is a hereditary disease caused by a
mutation in the gene that codes for a muscle protein called
dystrophin. Dystrophin is a key structural protein that helps to keep
muscle cells intact. DMD is characterized by a chronic degeneration
of skeletal muscle cells that leads to progressive muscle weakness.
Although intense research has focused on finding a way to replace the
defective dystrophin protein, at this time there is no cure for DMD.
A research group led by Dr. Yvan Torrente from the University of
Milan used a combination of cell- and gene-based therapy to isolate
adult human stem cells from DMD patients and engineer a genetic
modification to correct the dystrophin gene. "Use of the patient's
own cells would reduce the risk of implant rejection seen with
transplantation of normal muscle-forming cells," explains Dr.
Torrente.
Muscle stem cells, identified by expression of the CD133 surface
marker, were isolated from normal and dystrophic human blood and
skeletal muscle. The isolated human muscle progenitors were implanted
into the muscles of mice and were successfully recruited into muscle
fibers. As expected, the CD133+ cells isolated from DMD patients
expressed the mutated gene for dystrophin and gave rise to muscle
cells that resembled muscle fibers in DMD patients.
The researchers then used a sophisticated genetic technique to repair
the mutated dystrophin gene in the isolated DMD CD133+ cells so that
dystrophin synthesis was restored. Importantly, intramuscular or
intra-arterial delivery of the genetically corrected muscle cell
progenitors resulted in significant recovery of muscle morphology,
function, and dystrophin expression in a mouse model of muscular
dystrophy.
"These data demonstrate that genetically engineered blood or muscle-
derived CD133+ cells represent a possible tool for future stem cell-
based autograft applications in humans with DMD," says Dr. Torrente.
The authors caution that significant additional work needs to be done
prior to using this technology in humans. "Additional research will
substantially enhance our understanding of the mechanisms underlying
this effect and may lead to the improvement of gene and cell therapy
strategies for DMD."
###
The researchers include Rachid Benchaouir, Mirella Meregalli, Andrea
Farini, Marzia Belicchi, Maurizio Battistelli, and Nereo Bresolin, of
the University of Milan, in Milan, Italy; Yvan Torrente of the
University of Milan, in Milan, Italy, and UNISTEM, at University of
Milan, in Milan, Italy; Giuseppe D'Antona and Roberto Bottinelli, of
the Human Physiology Unit, University of Pavia, in Pavia, Italy;
Aure´ lie Goyenvalle, of Genethon-CNRS, in Evry, France; and Luis
Garcia, of Genethon-CNRS, in Evry, France.
Public release date: 12-Dec-2007
Contact: Cathleen Genova
cgenova@cell.
617-397-2802
Cell Press
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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