Stem-cell transplantation prompts muscle growth in mice with muscular dystrophyJanuary 21st, 2008 - 1:53 pm ICT by admin
London, January 21 (ANI): Researchers at the University of Texas Southwestern Medical Center have successfully used embryonic stem cells from mice to prompt the growth of healthy muscle cells in the rodents afflicted with a human model of Duchenne muscular dystrophy.
This is the first time that transplanted embryonic stem cells have been shown to restore function to defective muscles in an animal model of muscular dystrophy.
The researchers have revealed that their novel procedure involves stringent sorting to preserve all stem cells destined to become muscle.
Upon experimentation, the researchers found that their technique avoided the risk of tumour formation while improving the overall muscle strength and coordination of the mice.
Just like humans suffering from the fatal wasting disease, the mice used in the study also lacked a protein called dystrophin.
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, Nature Medicine quoted Dr. Rita Perlingeiro, assistant professor of developmental biology and molecular biology, as saying.
These cells can be transplanted into the muscle, and they cause muscle regeneration resulting in stronger contractility, added Dr. Perlingeiro, who headed the study.
She considers her work to be a landmark study because the researchers were able to tease out exactly the cells they wanted.
The problem had been that embryonic stem cells make everything. They make a great variety of cells. The trick is to pull out only the one type you want, Dr. Perlingeiro said.
During the study, the research team focused on manipulating genes that are active in the very early stages as embryonic stem cells start to develop into more specialized cells. They first activated a gene called Pax3, which is involved in creating muscle cells, and then injected those cells into the animals muscles.
Such cells caused tumours containing many different types of cells, suggesting that there were still residual undifferentiated embryonic stem cells in the cultures at the time of implantation.
Even if there are 10 undesirable cells, thats too many, Dr. Perlingeiro said.
The researchers later started using fluorescent dyes to sort cells depending on whether some surface markers were turned on while others were turned off.
They said that the process was similar to choosing people with red hair, green scarves and blue coats from a crowd, while disqualifying those without coats.
Having made the final selection of cells, containing only one type, the researchers once again injected them into the animals hind-limb muscles.
One month later, the fluorescent dyes showed that the cells had deeply penetrated the muscle, suggesting that they were growing and reproducing as desired. Many of the muscle fibres also contained dystrophin.
The mice did not show any signs of tumours even three months after the treatment.
Upon tests, it was found that the treated muscles were significantly stronger than those of untreated mice lacking dystrophin, although not quite as strong as those of normal mice. When tested for co-ordination, the treated mice performed better than that of untreated mice, but not as good as normal mice.
The improved coordination is significant because it shows the embryonic stem cells have benefited the animals quality of life, not simply caused an isolated growth with no overall improvement, Dr. Perlingeiro said.
The researchers are now planning a study to determine whether 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. (ANI)
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