Chuck Bednar for redOrbit.com – Your Universe Online
Researchers may soon test new drugs and study diseases in functioning human muscles thanks to Duke University, where biomedical engineers have, for the first time, grown contracting human muscles in a laboratory.
The researchers explain in a statement that the lab-grown muscles respond to external stimuli such as electrical pulses, biochemical signals, and pharmaceuticals just like native tissue. The findings of the study have been published in the Tuesday edition of the open-access journal, eLife.
“The beauty of this work is that it can serve as a test bed for clinical trials in a dish,” explained study author and associate professor of biomedical engineering, Nenad Bursac. “We are working to test drugs’ efficacy and safety without jeopardizing 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, along with postdoctoral researcher Lauran Madden, started with a small sample of human cells that had already progressed beyond the stem cell stage, but had not yet formed into muscle tissue. They expanded these “myogenic precursors” by more than 1000-fold, and then placed them into supporting 3D scaffolding filled with a nourishing gel.
That gel, the study authors explained, allowed them to form aligned and functioning muscle fibers. The new muscles were then subjected to a series of tests to determine how closely they resemble native tissue inside a human body. The researchers found that they contracted in response to electrical stimuli – something that had never happened in lab-grown muscles before.
Furthermore, they also demonstrated that the signaling pathways allowing nerves to activate the muscles were intact and functional. To determine if it could be used as a proxy for medical tests, Bursac and Madden subjected it to several different drugs, including cholesterol-lowering statins and the performance-enhancing drug clenbuterol.
The effects of the drugs matched those observed in human patients, the researchers said. The statins had a dose-dependent response and caused abnormal fat accumulation at high doses. The clenbuterol displayed a narrow beneficial window for increased contraction. Both effects have been observed in actual patients, and unlike in the muscle tissue of laboratory mice, clenbuterol was found to be capable of harming rodents at specific doses.
“We have a lot of experience making bioartifical muscles from animal cells in the laboratory,” Madden said, “and it still took us a year of adjusting variables like cell and gel density and optimizing the culture matrix and media to make this work with human muscle cells.”
“One of our goals is to use this method to provide personalized medicine to patients,” Bursac added. “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 is reportedly working with clinical researchers to try and correlate drug efficacy in patients with the effects on the lab-grown muscles. The study authors are also trying to use using induced pluripotent stem cells to grow the contracting muscle tissue instead of biopsied cells.
“There are a some diseases, like Duchenne Muscular Dystrophy for example, that make taking muscle biopsies difficult. If we could grow working, testable muscles from induced pluripotent stem cells, we could take one skin or blood sample and never have to bother the patient again,” Bursac said.
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