Unique population of muscle stem cells found in mice

May 20, 2002

PITTSBURGH, May 21 - Transplanting a unique population of muscle stem cells from healthy newborn mice delivers dystrophin, a key protein for muscle function, into mice born with a genetic muscle-wasting disease similar to Duchenne muscular dystrophy, Johnny Huard, Ph.D., and his colleagues report in the May 27 issue of the Journal of Cell Biology. The text is available online now at http://www.jcb.org.

"Studying the behavior of these cells after transplant, we found some very exciting things," said Dr. Huard, who is an associate professor of orthopaedic surgery, molecular genetics, biochemistry and bioengineering at the University of Pittsburgh School of Medicine and director of the Growth and Development Laboratory at Children's Hospital of Pittsburgh. "Not only did the donor cells continue to grow and make dystrophin in the recipient, but they also apparently failed to provoke an immune response, which would protect them from rejection."

Dr. Huard, Zhuqing Qu-Peterson, Ph.D., and other colleagues from the University of Pittsburgh and the University of Bonn, Germany, isolated stem cells from the muscle of healthy newborn mice that had been grown in culture.

Using a technique called pre-plating, the dividing cells were culled into differing groups and eventually winnowed to what Dr. Huard calls muscle-derived stem cells or MDSC. These cells were injected into the muscles of "mdx" mice, a rodent model for Duchenne muscular dystrophy. In humans, this disease causes muscle weakness and early death because of respiratory or cardiac failure.

Dr. Huard and his colleagues are working on the transplantation of MDS cells as a potential approach to deliver dystrophin to the muscles of mdx mice. Less refined muscle cells, called EP (early plate) cells, also were transplanted into mdx mice for comparison.

"These muscle-derived stem cells appear to be pluripotent; they can differentiate into muscle, neural and vascular lineages both in vitro and in vivo," said Dr. Huard, who also is deputy director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. "In addition, we were able to use a gene marker to prove that these cells were incorporated into the musculature of mdx mice. The cells continued to proliferate, make dystrophin and improve muscle regeneration."

MDS cells were "tagged" with the LacZ reporter gene and traced, Dr. Huard explained, adding that these marked cells were found in blood vessels and peripheral nerve tissue as well as in muscle tissue. Researchers also looked for evidence of immune system activity at the transplant sites and monitored cell activity for three months.

"These results suggest that the improved transplantation capacity of the MDSC may be attributed to their inability to trigger infiltration of activated lymphocytes ... which would eventually play a role in immune rejection of the transplanted cells," Dr. Huard wrote.

While these results are promising, further investigation is necessary. Scientists still have not identified a way to deliver the missing dystrophin gene systemically to achieve a global improvement in muscle function.

"We need to find out the best way to make these cells grow and become the right kinds of cells, as well as to control the process," said Dr. Huard. "But it is an important step in the development of muscle cell transplantation for Duchenne muscular dystrophy patients."

In addition to Drs. Huard and Qu-Peterson, other authors are Bridget Deasy, Ron Jankowski, Makato Ikezawa, M.D., James Cummins, Ryan Pruchnic, John Mytinger, Baohong Cao, M.D., Ph.D., and Charley Gates, all of the University of Pittsburgh; and Anton Wernig, M.D., Ph.D., of the University of Bonn, Germany.

Michele D. Baum
UPMC News Bureau
PHONE: 412-647-3555
E-MAIL: BaumMD@msx.upmc.edu

Melanie Finnigan
Children's Hospital of Pittsburgh
PHONE: 412-692-5016
E-MAIL: Melanie.Finnigan@chp.edu

University of Pittsburgh Medical Center

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