Tissue Engineering of a Section of Contracting Muscle

Researchers are making further progress towards fully functional muscle tissue grown from cells, though at this point the principal use for such engineered tissue is in research rather than treatment. Scaling up the size of the tissue produced remains a tough challenge due to the need to produce complex blood vessel networks within the engineered tissue. This is why techniques such as decellularization of a donor organ are making headway, as that provides a scaffold complete with a framework for blood vessels and the chemical cues needed to guide cells to repopulate them, something that cannot yet be produced from scratch:

Researchers 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 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 fibers. "We have a lot of experience making bioartifical muscles from animal cells in the laboratory, 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."

Researchers subjected the new muscle to a barrage of tests to determine how closely it resembled native tissue inside a human body. They found that the muscles robustly contracted in response to electrical stimuli - a first for human muscle grown in a laboratory. They also showed that the signaling 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, the researchers 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.

Link: http://www.pratt.duke.edu/news/first-contracting-human-muscle-grown-laboratory

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