Science

Working human muscle tissue grown from skin-derived stem cells

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A cross section of a muscle fiber grown from induced pluripotent stem cells.
Duke University
A cross section of a muscle fiber grown from induced pluripotent stem cells.
Duke University
A stained cross section of the new muscle fibers – the red cells are muscle cells, the green areas are receptors for neuronal input, and the blue patches are cell nuclei
Duke University

Back in 2015, a team at Duke University made a world-first breakthrough, growing functioning human muscle tissue in a laboratory using cells from muscle biopsies called myogenic precursors. Now the research has leapt forward with working muscle being successfully grown from scratch using pluripotent stem cells.

Pluripotent stem cells have the potential to turn into almost any cell in the body and research over the last decade has uncovered remarkable techniques allowing scientists to reprogram human skin cells into pluripotent stem cells.

"Starting with pluripotent stem cells that are not muscle cells, but can become all existing cells in our body, allows us to grow an unlimited number of myogenic progenitor cells," says Nenad Bursac, one of the authors on the study.

To kickstart the stem cells' transformation into muscle cells, the researchers recruited a protein called Pax7. This molecule signals to the stem cells to start turning into muscle tissue and, using a 3D matrix, the cells then grow into functioning muscle fibers that respond to external stimuli in the same way as natural muscle tissue would.

"It's taken years of trial and error, making educated guesses and taking baby steps to finally produce functioning human muscle from pluripotent stem cells," says Lingjun Rao, first author of the study. "What made the difference are our unique cell culture conditions and 3-D matrix, which allowed cells to grow and develop much faster and longer than the 2-D culture approaches that are more typically used."

A stained cross section of the new muscle fibers – the red cells are muscle cells, the green areas are receptors for neuronal input, and the blue patches are cell nuclei
Duke University

The muscle tissue was successfully implanted into adult mice and effectively functioned as it was progressively integrated into the native tissue for at least three weeks. The initial drawback noted in the study was that the new muscle tissue was not as strong as the muscle tissue previously grown from muscle biopsies in earlier studies or native muscle tissue.

However, the researchers note that this stem cell-derived muscle still holds promise for future uses, not necessarily to replace a person's diseased muscle entirely, but to aid small-scale localized muscle regrowth and to create personalized lab-grown muscles that can test the effects of drugs on the anatomy of specific patients.

"The prospect of studying rare diseases is especially exciting for us," says Bursac. "When a child's muscles are already withering away from something like Duchenne muscular dystrophy, it would not be ethical to take muscle samples from them and do further damage. But with this technique, we can just take a small sample of non-muscle tissue, like skin or blood, revert the obtained cells to a pluripotent state, and eventually grow an endless amount of functioning muscle fibers to test."

The research was published in the journal Nature Communications.

Source: Duke University

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