Researchers have for the first time grown human skeletal muscle in the lab which contracts and responds just like native tissue to external stimuli such as electrical pulses, biochemical signals and pharmaceuticals. The lab-grown tissue will allow researchers to test new drugs and study diseases in functioning human muscle outside of the human body to provide personalised medicine to patients.
“The beauty of this work is that it can serve as a test bed for clinical trials in a dish,” said Nenad Bursac, associate professor of biomedical engineering at Duke University, who led the study with Lauran Madden, a postdoctoral researcher in Bursac’s laboratory. “We are working to test drugs’ efficacy and safety without jeopardising a patient’s health and also to reproduce the functional and biochemical signals of diseases -especially rare ones and those that make taking muscle biopsies difficult,” Bursac said.
Bursac and Madden started with a small sample of human cells that had already progressed beyond stem cells but hadn’t yet become muscle tissue. They expanded these “myogenic precursors” by more than a 1000-fold, and then put them into a supportive, 3D scaffolding filled with a nourishing gel that allowed them to form aligned and functioning muscle fibres.
Madden subjected the new muscle to a barrage of tests to determine how closely it resembled native tissue inside a human body. She found that the muscles robustly contracted in response to electrical stimuli - a first for human muscle grown in a laboratory. She also showed that the signalling pathways allowing nerves to activate the muscle were intact and functional.
To see if the muscle could be used as a proxy for medical tests, Bursac and Madden studied its response to a variety of drugs, including statins used to lower cholesterol and clenbuterol, a drug known to be used off-label as a performance enhancer for athletes. The effects of the drugs matched those seen in human patients. The statins had a dose-dependent response, causing abnormal fat accumulation at high concentrations. Clenbuterol showed a narrow beneficial window for increased contraction. Both of these effects have been documented in humans.
Clenbuterol does not harm muscle tissue in rodents at those doses, showing the lab-grown muscle was giving a truly human response. “One of our goals is to use this method to provide personalised medicine to patients,” said Bursac.
“We can take a biopsy from each patient, grow many new muscles to use as test samples and experiment to see which drugs would work best for each person,” Bursac added. The study appears in the journal eLife. PTI
