Muscle is one of the most regenerative organs in the body, and it is bustling with adult stem cells standing ready to repair the many rips and disruptions that occur from exercise. Researchers have long struggled with a mystery, however. When they cultivate muscle stem cells in a dish, the cells often lose their ability to differentiate into muscle cells. Depending on the growth conditions, the artificially produced muscle loses its innate capacity to repair itself.
Duke University’s Nenad Bursac believes he may have found the solution. The key is to create a niche, 3-D microenvironment that encourages some cells to become muscle fibers and others to go into what he calls a “quiescent state.”
“They don’t do much, but if there’s an injury, they jump in, they proliferate, and they rebuild the muscle,” says Bursac, a professor of bioengineering. He hopes that one day his technique can be used to help treat patients with muscular dystrophy, in which their bodies attack their own muscle.
Stem cell source: Bursac obtains muscle through a biopsy, soaks the cells in a cocktail of factors and then adds some to a 3-D environment, a hydrogel that mimics the geometrical shape of a blood clot. This primes the cells to fuse, causing some to quickly become muscle fibers and others to stick to those fibers and remain stem cells in their quiescent states.
“Through this kind of a combination of things,” Bursac explains, “we managed to get tissue-engineered muscle but with a capacity to have a stem cell function and be able to regenerate the muscle after injury.”
In the pharmaceutical industry, new stem cell technologies are allowing scientists to examine brain disease in the petri dish while also testing the effectiveness and safety of potential drugs in new ways.
“You just don’t have access to the brain cells of 500 children with autism,” says Ricardo Dolmetsch, the global head of neuroscience at the Novartis Institutes for BioMedical Research. “The next best thing is to make them.”
Dolmetsch is using iPS cells to study psychiatric and neurodegenerative diseases, and to screen for drugs that might work to treat them. He and his colleagues take skin cells or blood cells from those with the conditions they wish to study. They turn those cells into stem cells and coax them to become neurons. Because every cell from an individual carries the same genetic blueprint, these neurons should be identical to the neurons in each patient’s brain — and should carry the same defects that spur disease. They can then be used to test drug interventions or to test hypotheses about the causes of disease.
“Now that we have the capacity to make cells for many, many people in an automated way, we can effectively do a kind of clinical trial on their cells before we actually expose the patient to the drug,” Dolmetsch says. “Ultimately, it should allow us to produce less expensive drugs, more quickly.”
Stem cell source: Obtained from skin or blood cells of patients. These samples are then infected with modified viral vectors, essentially re-engineered to contain pieces of DNA that activate specific genes and cause the samples to behave like embryonic stem cells. Dolmetsch exposes these stem cells to a variety of different growth factors that mimic those that induce stem cells to become neurons during normal development.