Harvard Zebrafish Research Yields Possible Treatments for Muscle Diseases

Harvard Zebrafish Research Yields Possible Treatments for Muscle Diseases

Zebrafish experiments by Harvard University researchers yielded new chemicals that prod stem cells to make muscle tissue, an advance 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 today 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 would most likely be used first in patients with battlefield wounds or other trauma that sometimes 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 the animals lay 200 eggs every week. Using a similar approach to research in fish, Zon previously developed a method of increasing cord blood cells for transplantation into babies that recently cleared an initial step in human trials.

Unmet Need

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

“The discoveries made in one model system are validated across model systems and then effectively translated all the way to human derived tissue,” 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

Six chemicals emerged that had the strongest effect of steering the cells to make satellite cells, a type that specifically builds muscle tissue. 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, a patient advocacy group. “Second, the researchers identified agents that could stimulate these satellite cells to develop into mature muscle fibers.”

Zon made the human muscle cells from a type of stem cell that can be produced from any individual’s skin or blood. These are induced pluripotent stem cells — human skin cells that have been reprogrammed by genes to behave like the powerful stem cells that can make any of the body’s tissues.

Much work remains before such tissues could be used in humans, Muhlrad said. However, the method of programming cells to become different tissues could be applied widely, Zon said.

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

To contact the reporter on this story: John Lauerman in Boston at jlauerman@bloomberg.net

About bambooinnovator
Kee Koon Boon (“KB”) is the co-founder and director of HERO Investment Management which provides specialized fund management and investment advisory services to the ARCHEA Asia HERO Innovators Fund (www.heroinnovator.com), the only Asian SMID-cap tech-focused fund in the industry. KB is an internationally featured investor rooted in the principles of value investing for over a decade as a fund manager and analyst in the Asian capital markets who started his career at a boutique hedge fund in Singapore where he was with the firm since 2002 and was also part of the core investment committee in significantly outperforming the index in the 10-year-plus-old flagship Asian fund. He was also the portfolio manager for Asia-Pacific equities at Korea’s largest mutual fund company. Prior to setting up the H.E.R.O. Innovators Fund, KB was the Chief Investment Officer & CEO of a Singapore Registered Fund Management Company (RFMC) where he is responsible for listed Asian equity investments. KB had taught accounting at the Singapore Management University (SMU) as a faculty member and also pioneered the 15-week course on Accounting Fraud in Asia as an official module at SMU. KB remains grateful and honored to be invited by Singapore’s financial regulator Monetary Authority of Singapore (MAS) to present to their top management team about implementing a world’s first fact-based forward-looking fraud detection framework to bring about benefits for the capital markets in Singapore and for the public and investment community. KB also served the community in sharing his insights in writing articles about value investing and corporate governance in the media that include Business Times, Straits Times, Jakarta Post, Manual of Ideas, Investopedia, TedXWallStreet. He had also presented in top investment, banking and finance conferences in America, Italy, Sydney, Cape Town, HK, China. He has trained CEOs, entrepreneurs, CFOs, management executives in business strategy & business model innovation in Singapore, HK and China.

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