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Zebrafish experiments yield chemicals that coax stem cells to make muscle

– Zebrafish experiments by Harvard University researchers yielded chemicals that prod stem cells to make muscle tissue, a discovery that may lead to treatments for muscular dystrophy and related disorders.

The chemicals, found to coax fish embryo cells to form muscle, also had the same effect on human stem cells that were transplanted into mice with a muscle-wasting disease.

The researchers’ findings were published Thursday in the journal Cell.

The discovery of the growth-spurring chemicals may offer a template for devising efficient ways to make other tissues, such as kidney and liver, from stem cells, said Leonard Zon, a Harvard stem cell scientist at Boston Children’s Hospital and one of the leaders of the study.

“Understanding how to turn reprogrammed cells into tissues for transplantation is one of the biggest goals of this field,” he said in a telephone interview. “We’ve made muscle cells, and there are probably many more tissues that we might be able to make.”

While the use of reprogrammed muscle tissue might be years off, it most likely would be used first in patients with battlefield wounds or other trauma that results in muscle atrophy, Zon said.

Treating muscular dystrophy, a genetic disease that causes gradual muscle weakness and wasting, would be a later goal, he said.

Zon focuses on zebrafish, which speed the study of stem cells because they lay 200 eggs every week.

The Harvard experiment attacks “a major unmet need” in producing human cells that may be used to study and perhaps treat a number of muscle disorders, said Andre Terzic, director of the Mayo Clinic’s Center for Regenerative Medicine in Rochester, Minn.

Showing that the same drugs work in cells from several species also bolsters the findings, he said.

In his experiment, Zon grew the eggs into an embryonic stage, where all the cells remained stem cells that can differentiate into any cell in the body. Normally, the embryonic cells would develop into the variety of tissues needed to make a zebrafish.

Zon put the groups of cells into dishes and treated them with 2,400 different chemicals known to affect growth and development.

Six chemicals emerged that had the strongest effect of steering the cells to make satellite cells, a type that specifically builds.

Zon used the same chemicals to make muscle tissue from human stem cells.

Amy Wagers, a stem cell scientist at Harvard and the Joslin Diabetes Center who co-wrote the paper, grafted the muscle into mice that had been bred to develop muscular dystrophy.

“Since satellite cells are relatively sparse in the body, this could provide a means to producing expanded numbers of muscle-generating cells for medical applications,” said Paul Muhlrad, director of basic research for the Muscular Dystrophy Association.

Zon made the human muscle cells from a type of stem cell that can be produced from any individual’s skin or blood.

Much work remains before such tissues could be used in humans, but the method of programming cells to become different tissues could have wide application.

“It’s very generalizable,” Zon said. “A lot of people are excited.”