Muscle built in diseased mice: Human muscle cells created in a dish

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Muscle built in diseased mice: Human muscle cells created in a dish

Skeletal muscle has proved to be very difficult to grow in patients with muscular dystrophy and other disorders that degrade and weaken muscle. Researchers now report boosting muscle mass and reversing disease in a mouse model of Duchenne muscular dystrophy, using a “cocktail” of three compounds identified through a new rapid culture system. Adding the same compounds to stem cells derived from patients’ skin cells, they then successfully grew human muscle cells in a dish.

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Nov. 7, 2013 — Skeletal muscle has proved to be very difficult to grow in patients with muscular dystrophy and other disorders that degrade and weaken muscle. Researchers at Boston Children’s Hospital’s Stem Cell Program now report boosting muscle mass and reversing disease in a mouse model of Duchenne muscular dystrophy, using a “cocktail” of three compounds identified through a new rapid culture system. Adding the same compounds to stem cells derived from patients’ skin cells, they then successfully grew human muscle cells in a dish.Senior investigator Leonard Zon, MD, director of the Stem Cell Program at Boston Children’s and an investigator with the Howard Hughes Medical Institute, hopes for clinical trials to begin transplanting these cells into patients with muscle loss in the next several years. In the meantime, the screening technique, described in the journal Cell (published online November 7), can also be applied to multiple disorders beyond muscular dystrophy, he says.#1: ZebrafishThe drug screening technique begins with zebrafish. Zon and colleagues placed tiny zebrafish blastomeres — cells from very early stage embryos — into 384-well culture dishes, adding one test compound to each well. This allowed them to screen 2,400 compounds at once, seeking ones that boosted numbers of muscle progenitor cells in the see-through fish as they developed.The Zon Lab’s earlier work with zebrafish led to a drug derived from prostaglandin that expands numbers of blood stem cells and is now in a Phase II clinical trial. But this time, researchers genetically modified the fish so that newly created muscle progenitor cells would show up in fluorescent green, and muscle fibers in red. This enabled the team to rapidly quantify muscle cells and fibers produced under different conditions, based on visual readouts — without having to examine each well’s contents through laborious biochemical techniques.”Automated imagers can take a picture to assay all the 384 wells within a matter of a week, as compared with several months with our earlier technique,” says Zon, who is also a member of Boston Children’s Division of Hematology/Oncology as well as the Harvard Stem Cell Institute (HSCI).#2: MiceThe zebrafish tests revealed six compounds that expanded numbers of skeletal muscle progenitor cells. The Zon Lab collaborated with Amy Wagers, PhD, of HSCI and the Joslin Diabetes Center, and C. …

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Muscle built in diseased mice: Human muscle cells created in a dish

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