Muscle stem cells and fibers can be grown in the lab from reprogrammed connective tissue cells (microscopy image). Credit: ETH Zurich/ Bar- Nur lab
Teacher Ori Bar-Nur and his coworkers at ETH Zurich are pioneering the cultivation of muscle cells in the laboratory, currently using mouse cells as their primary design. The ramifications of their research study are manifold: lab-cultured human muscle tissue could serve surgical requirements, while human muscle stem cells might offer healing options for those with muscle diseases.
In the meantime, nevertheless, the ETH teams research is focused on optimizing the generation of muscle stem cells and making it much safer. They have now succeeded in doing so by means of a new approach.
Reprogrammed cells.
Like other scientists in the field, the researchers at ETH Zurich use a different, easier-to-grow cell type as the beginning material for producing muscle cells: connective tissue cells. Utilizing a cocktail of little molecules and proteins, they molecularly “reprogram” these cells, therefore converting them into muscle stem cells, which then multiply quickly and produce muscle fibers.
” This approach enabled us to produce large quantities of muscle cells,” describes Xhem Qabrati, a doctoral trainee in the Bar- Nur group and one of two lead co-authors on this research study. “Although muscle cells could also be cultured straight from muscle biopsies, the cells tend to lose their performance after isolation, rendering it challenging to produce large amounts of cells.”
MyoD is not usually present in connective tissue cells. Before these cells can turn into muscle cells, researchers have to coax them to produce MyoD in their nucleus for a number of days.
No genetic engineering
Previously, scientists have turned to genetic engineering for this process: They used viral particles to carry the DNA plan for the MyoD protein into the cell nucleus. There, the infections insert these structure guidelines into the genome, allowing the cells to produce the MyoD protein.
This approach carries a security risk: researchers can not control where exactly in the genome infections insert these instructions. In some cases the viruses integrate into the middle of a crucial gene, damaging it, or this insertion procedure may lead to changes that can activate cancer cell development.
This time, Bar-Nur and his colleagues used a different technique to provide MyoD to connective tissue cells, influenced by the mRNA vaccines for COVID-19: instead of utilizing viruses to introduce the DNA plan of the MyoD gene, they introduce the mRNA records of this gene into cells.
Given that this leaves the cells genome unchanged, it prevents the negative repercussions associated with such modifications. The mRNA still enables the connective tissue cells to produce the MyoD protein, such that– together with the other elements of the mixed drink optimised by the ETH researchers– they can become muscle stem cells and fibers.
The scientists just recently published their new technique in the journal NPJ Regenerative Medicine. They are the very first to reprogram connective tissue cells into muscle stem cells without hereditary engineering.
Aid with muscle dystrophy
The muscle cells produced in this manner are likewise completely functional, as the scientists have actually displayed in explores mice struggling with Duchenne muscular dystrophy. In humans, this unusual hereditary illness leaves sufferers lacking a protein needed for muscle stability, implying they experience progressive muscle wasting and paralysis.
The ETH Zurich scientists injected non-defective muscle stem cells into the muscles of Duchenne muscular dystrophy mice carrying this flaw. They were able to show that the healthy stem cells form repaired muscle fibers in the muscles.
” Muscle stem cell transplantation of this sort might be particularly useful for patients with innovative Duchenne, who are already seriously affected by muscle atrophy,” describes Inseon Kim, another doctoral trainee in the Bar-Nur group and a lead co-author on this research study.
The method is appropriate for producing big quantities of muscle stem cells needed for this purpose. Whats more, the reality that it does so without genetic modification and the associated risks makes it appealing for possible future therapeutic usage in humans.
Alternative meat production
The researchers have yet to adjust their method to human cells; this is their next action. “In addition, we want to examine whether its also possible to convert connective tissue cells into muscle cells directly in the body by injecting the MyoD mRNA and the other mixed drink parts into mice affected by muscle illness,” Bar-Nur says. This approach, too, may one day help human patients.
Bar-Nur and his team would like to integrate their brand-new findings into their ongoing work with cow cells– another research study stream of the laboratory. They hope this method would help current efforts to culture animal muscle stem cells for cultivated meat production, an alternative approach to produce meat for consumption.
Referral: “Transgene-free direct conversion of murine fibroblasts into practical muscle stem cells” by Xhem Qabrati, Inseon Kim, Adhideb Ghosh, Nicola Bundschuh, Falko Noé, Andrew S. Palmer and Ori Bar-Nur, 8 August 2023, npj Regenerative Medicine.DOI: 10.1038/ s41536-023-00317-z.
Teacher Ori Bar-Nur and his coworkers at ETH Zurich are pioneering the growing of muscle cells in the lab, currently using mouse cells as their main model. The implications of their research study are manifold: lab-cultured human muscle tissue could serve surgical requirements, while human muscle stem cells may provide healing solutions for those with muscle diseases. MyoD is not usually present in connective tissue cells. Before these cells can turn into muscle cells, researchers have to coax them to produce MyoD in their nucleus for numerous days.
“In addition, we wish to examine whether its also possible to convert connective tissue cells into muscle cells straight in the body by injecting the MyoD mRNA and the other cocktail elements into mice impacted by muscle illness,” Bar-Nur says.
