Breeding success in laboratory muscles

Muscle stem cells and fibers can now be cultivated in the laboratory without genetic engineering. Micrograph © ETH Zurich / Bar-Nur Lab

Researchers have made important progress on the way to new muscle wasting therapies and animal-free meat production: they present an innovative method for mass-cultivating muscle tissue in the laboratory. The transformation of connective tissue cells into muscle stem cells is possible without genetic engineering. Instead, a process that is also used in Covid mRNA vaccines ensures the transformation, the scientists report.

They get our body going in a variety of ways: if muscles become excessively weak or are massively degraded due to certain illnesses, there is a risk of disabilities or even death. In order to be able to help build muscle mass in these cases, researchers have been exploring ways of growing muscles or muscle stem cells in the laboratory for some time. The vision is that the tissue obtained could be used in surgery or the muscle-building units could be administered to people with certain diseases. In addition to these medical applications, however, the process also has another interesting potential: It could provide meat for which no animals have to be slaughtered.

In principle, muscle cultivation already works in the laboratory: the starting material is formed by connective tissue cells, because they ultimately lead to more muscle mass than if the material from muscle biopsies is used. In order to produce the target tissue, the connective tissue cells have so far been reprogrammed using genetic engineering and a cocktail of active substances and proteins. A central factor is the protein MyoD. It is a so-called transcription factor that regulates the activity of certain genes that lead to the transformation into muscle stem cells.

Tissue breeding without genetic engineering

In order to trigger the process artificially, MyoD must be produced in the connective tissue cells for several days. So far, this has been achieved by modifying the genetic material of the cells: the blueprint for the production of MyoD is inserted into the genetic material using genetic engineering methods. However, such methods are notoriously problematic. This is because these are genetically modified cells and the resulting muscle material is also shaped by the manipulations.

The new method developed by the research team from the Swiss Federal Institute of Technology in Zurich (ETH) is now addressing this critical aspect. The scientists were inspired by the Covid mRNA vaccines to provide the genetic material for the production of MyoD in the connective tissue cells. The building instructions for immune-stimulating proteins are introduced into cells without changing the genetic material. Accordingly, the researchers have now used the method to introduce the mRNA copy of this assembly manual into the cells instead of the DNA sequence of MyoD. The genome of the cells remains unchanged, which is why there are no associated negative consequences. Nevertheless, thanks to the mRNA, the treated connective tissue cells are able to produce the protein MyoD in sufficient quantities. In combination with other adapted components of the process, they can thus successfully transform into muscle stem cells and fibers, the researchers report.

Potential for therapies and alternative meat production

They have also already been able to document that the muscle cells produced in this way are functional. To do this, the team generated muscle stem cells from mice. They were then used in model animals suffering from Duchenne muscular dystrophy. In humans, this hereditary disease leads to progressive muscle wasting and paralysis. As the team reports, after the muscle stem cells were injected into the muscles of the Duchenne mice, they developed functional muscle fibers there. This success now gives hope for new treatment options: "Such a muscle stem cell transplantation could be of particular interest for Duchenne patients in an advanced stage who are already severely affected by muscle atrophy," says co-first author Inseon Kim from ETH.

But until then, further development work is necessary, the researchers emphasize: Above all, they must now transfer their approach to human cells. They also want to pursue another interesting perspective: "We want to investigate whether connective tissue cells can be transformed into muscle cells directly in the body by injecting the MyoD mRNA and the other cocktail components into mice affected by a muscle disease," says Senior -Author Ori Bar-Nur from ETH. This strategy could also benefit people with muscle diseases.

The researchers also want to dedicate themselves to the potential of the method for the production of meat without animal suffering: Specifically, the new possibilities are now to be incorporated into the cultivation of cattle cells in the laboratory.

Source: Swiss Federal Institute of Technology in Zurich, specialist article: Nature, NPJ Regenerative Medicine doi: 10.1038/s41536-023-00317-zcall_made

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