Engineers grow functioning human muscle from skin cells

January 9, 2018, Duke University
Engineers grow functioning human muscle from skin cells

Biomedical engineers have grown the first functioning human skeletal muscle from induced pluripotent stem cells.

The advance builds on work published in 2015 when researchers at Duke University grew the first functioning human tissue from cells obtained from muscle biopsies. The ability to start from cellular scratch using non-muscle tissue will allow scientists to grow far more , provide an easier path to genome editing and cellular therapies, and develop individually tailored models of rare muscle diseases for drug discovery and basic biology studies.

The results appear online Tuesday, January 9, in Nature Communications.

"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," said Nenad Bursac, professor of biomedical engineering at Duke University. "These progenitor cells resemble adult muscle stem cells called 'satellite cells' that can theoretically grow an entire muscle starting from a single cell."

In their previous work, Bursac and his team started with small samples of human cells obtained from muscle biopsies, called "myoblasts," that had already progressed beyond the stem cell stage but hadn't yet become mature . They grew these myoblasts by many folds and then put them into a supportive 3-D scaffolding filled with a nourishing gel that allowed them to form aligned and functioning human muscle fibers.

In the new study, the researchers instead started with human induced pluripotent stem cells. These are cells taken from adult non-muscle tissues, such as skin or blood, and reprogrammed to revert to a primordial state. The pluripotent stem cells are then grown while being flooded with a molecule called Pax7—which signals the cells to start becoming muscle.

As the cells proliferated they became very similar to —but not quite as robust as—adult . While previous studies had accomplished this feat, nobody has been able to then grow these intermediate cells into functioning skeletal muscle.

The Duke researchers succeeded where previous attempts had failed.

Duke engineers have grown the first functioning human muscle from non-muscle cells -- skin cells reverted to their primordial stem cell state. The advance holds promise for cellular therapies, drug discovery and studying rare diseases. Credit: Duke University
"It's taken years of trial and error, making educated guesses and taking baby steps to finally produce functioning from pluripotent stem cells," said Lingjun Rao, a postdoctoral researcher in Bursac's laboratory and 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."

Once the cells were well on their way to becoming muscle, Bursac and Rao stopped providing the Pax7 signaling molecule and started giving the cells the support and nourishment they needed to fully mature.

In the study, the researchers show that after two to four weeks of 3-D culture, the resulting muscle cells form muscle fibers that contract and react to external stimuli such as electrical pulses and biochemical signals mimicking neuronal inputs just like native muscle tissue. They also implanted the newly grown muscle fibers into adult mice and showed that they survive and function for at least three weeks while progressively integrating into the native tissue through vascularization.

The resulting muscle, however, is not as strong as native muscle tissue, and also falls short of the muscle grown in the previous study that started from . Despite this caveat, the researchers say this muscle still holds potential that the stronger, older relative does not.

The pluripotent stem cell-derived muscle fibers develop reservoirs of "satellite-like cells" that are necessary for normal adult muscles to repair damage, while the muscle from the previous study had much fewer of these cells. The stem cell method is also capable of growing many more cells from a smaller starting batch than the biopsy method.

Both of the advantages point toward a possibility of using this new method for regenerative therapies and for creating models of rare diseases for future studies and individualized health care.

"The prospect of studying rare diseases is especially exciting for us," said 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 to a pluripotent state, and eventually grow an endless amount of functioning muscle fibers to test."

The technique also holds promise for being combined with genetic therapies. Researchers could, in theory, fix genetic malfunctions in the induced derived from a patient and then grow small patches of completely healthy muscle. While this could not heal or replace an entire body's worth of diseased muscle, it could be used in tandem with more widely targeted genetic therapies or to heal more localized problems.

The researchers are now refining their technique to grow more robust muscles and beginning work to develop new models of rare muscle diseases.

Explore further: Researchers create skeletal muscle from stem cells

More information: Lingjun Rao et al, Engineering human pluripotent stem cells into a functional skeletal muscle tissue, Nature Communications (2018). DOI: 10.1038/s41467-017-02636-4

Related Stories

Researchers create skeletal muscle from stem cells

December 18, 2017
UCLA scientists have developed a new strategy to efficiently isolate, mature and transplant skeletal muscle cells created from human pluripotent stem cells, which can produce all cell types of the body. The findings are a ...

Scientists reprogram stem cells to regenerate muscle in muscular dystrophy

December 22, 2017
Specially programmed stem cells demonstrated the potential to regenerate lost muscle mass in muscular dystrophy, according to a Northwestern Medicine study published in Nature Communications.

Regenerating muscle from stem cells

October 28, 2016
A microscopic image of a mouse leg that has been reconstructed with a stem cell transplant shows what may one day help patients regrow new muscle after a major surgery.

Beating heart patch is large enough to repair the human heart

November 28, 2017
Biomedical engineers at Duke University have created a fully functioning artificial human heart muscle large enough to patch over damage typically seen in patients who have suffered a heart attack. The advance takes a major ...

First contracting human muscle grown in laboratory

January 13, 2015
In a laboratory first, Duke researchers have grown human skeletal muscle that contracts and responds just like native tissue to external stimuli such as electrical pulses, biochemical signals and pharmaceuticals.

At the right place at the right time—new insights into muscle stem cells

September 17, 2012
Muscles have a pool of stem cells which provides a source for muscle growth and for regeneration of injured muscles. The stem cells must reside in special niches of the muscle for efficient growth and repair.

Recommended for you

Using light to stop itch

December 17, 2018
Itch is easily one of the most annoying sensations. For chronic skin diseases like eczema, it's a major symptom. Although it gives temporary relief, scratching only makes things worse because it can cause skin damage, additional ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Pain: Perception and motor impulses arise in brain independently of one another

December 13, 2018
Pain is a negative sensation that we want to get rid of as soon as possible. In order to protect our bodies, we react by withdrawing the hand from heat, for example. This action is usually understood as the consequence of ...

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.