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Stem Cells Used To Create Skeletal Muscle.

LOS ANGELES, Calif., December 18, 2017 -- Scientists here 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 major step towards developing a stem cell replacement therapy for muscle diseases, including Duchenne muscular dystrophy, which affects approximately one in 5,000 boys in the U.S. and is the most common fatal childhood genetic disease.

Researchers at the Eli and Edythe Broad Center at UCLA used the natural human development process as a guide, the researchers developed ways to mature muscle cells in the laboratory to create muscle fibers that restore dystrophin, the protein that is missing in the muscles of boys with Duchenne.

Without dystrophin, muscles degenerate and become progressively weaker. Duchenne symptoms usually begin in early childhood; patients gradually lose mobility and typically die from heart or respiratory failure around age 20. There is no way to reverse or cure the disease.

For years, scientists have been trying different methods that direct human pluripotent stem cells to generate skeletal muscle stem cells that can function appropriately in living muscle and regenerate dystrophin-producing muscle fibers.

However, the study found that the current methods are inefficient; they produce immature cells that are not appropriate for modeling Duchenne in the laboratory or creating a cell replacement therapy for the disease.

They found that just because a skeletal muscle cell produced in the lab expresses muscle markers, doesn't mean it is fully functional.

For a stem cell therapy for Duchenne to move forward, there must be a better understanding of the cells being generated from human pluripotent stem cells compared to the muscle stem cells found naturally in the human body and during the development process.

By analyzing human development, the researchers found a fetal skeletal muscle cell that is extraordinarily regenerative. Upon further analysis of these fetal muscle cells two new cell surface markers called ERBB3 and NGFR were discovered; this enabled the researchers to precisely isolate muscle cells from human tissue and separate them from various cell types created using human pluripotent stem cells.

Once they were able to isolate skeletal muscle cells using the newly identified surface markers, the research team matured those cells in the lab to create dystrophin-producing muscle fibers. The muscle fibers they created were uniformly muscle cells, but the fibers were still smaller than those found in real human muscle.

"We were missing another key component," said Michael Hicks, lead author of the study. The skeletal muscle cells were not maturing properly. "We needed bigger, stronger muscle that also had the ability to contract."

Once again, the team looked to the natural stages of human development for answers. A specific cell signaling pathway called TGF Beta needs to be turned off to enable generation of skeletal muscle fibers that contain the proteins that help muscles contract. Lastly, the team tested their new method in a mouse model of Duchenne.

The results were exactly what they'd hoped for. The study demonstrated that functional muscle cells can be created in a laboratory and restore dystrophin in animal models of Duchenne using the human development process as a guide.

The newly identified strategy to generate skeletal muscle from human pluripotent stem cells is covered by a patent application filed by the UCLA Technology Development Group on behalf of The Regents of the University of California, with Michael Hicks and April Pyle as co-inventors.

Citation: Michael R. Hicks et al., "ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs," Nature Cell Biology, 2017; DOI: 10.1038/s41556-017-0010-2


Contact: April Pyle,
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Title Annotation:Advanced Stem Cell Technology
Publication:Stem Cell Business News
Date:Jan 22, 2018
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