▎ WuXi AppTec content team editor
In a study published in the journal Cell Stem Cell, a team of researchers led by Johns Hopkins University School of Medicine grew self-renewing human muscle stem cells in vitro and used such cells to successfully repair damaged muscle tissue in mice. This breakthrough points to the potential direction for the treatment of muscle damage and sarcopenia in humans.
To prepare these self-renewing stem cells, the research team started with lab-grown human skin cells and transformed them into more primitive induced pluripotent stem cells (iPS cells) through gene editing, which have the potential to evolve into arbitrary cells in the body.
In fact, scientists have long been able to transform iPS cells into skin cells, brain cells, and many other different cells in the laboratory. But the more difficult question is how to turn iPS cells into stem cells that can renew themselves in specific organs.
To achieve this, in the latest study, the authors induced iPS cells into muscle stem cells using nutrient-rich and standard cell growth factors and media.
Subsequently, in mouse experiments, the research team examined how the newly cultured cells migrated in living animals and whether they could repair damaged tissue.
When they inject newly cultured muscle stem cells into the muscles of mice, they move into the muscle niche, where the mice' own muscle stem cells congregate. These stem cells remained in this area for at least 4 months.
▲Mouse muscle image: green is a muscle stem cell protein; red is human-specific lamin A/C (Image source: Sunny Sun)
Can these stem cells play a role in repairing damaged tissue? The authors used two different approaches to verify this problem.
First, the authors injected muscle stem cells into gene-edited mice that lacked a normal immune system and therefore avoided immune rejection caused by transplanted cells. The mice were subsequently exposed to toxins and radiation that caused muscle degradation, which cleared the body of existing muscle stem cells.
The researchers found that at the site of toxin and radiation damage to muscle tissue, transplanted muscle stem cells developed into myoblasts, which fused and developed into microfibers in normal muscles, successfully repairing muscle damage. They also found that some of the transplanted muscle stem cells behaved similarly to the mice's own muscle stem cells after migrating to stem cell niches.
Schematic diagram of the experimental design of the latest study (Image source: Reference[1])
In the second validation experiment, the researchers transplanted muscle stem cells into another gene-edited mouse. The mice had mutations in the genes that regulate dystrophin and therefore developed Duchenne muscular dystrophy.
The research team found that the transplanted muscle stem cells migrated to the stem cell niche area of the muscle. In months of experiments, transplanted mice ran twice as fast as non-transplanted mice in the roller test, reflecting stronger muscle strength.
"These muscle stem cells promise to provide new therapies for a wide range of muscle diseases." Professor Gabsang Lee, who led the study, noted.
Next, the team plans to further explore how to make this strategy work in mouse models with other muscle-related symptoms. We expect that in the future, this technology may be applied to the treatment of sports injuries, trauma and aging-related muscle loss, bringing new therapies to human patients."
Cover image source: 123RF
Resources:
[1] Congshan Sun et al, Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment, Cell Stem Cell (2022). DOI: 10.1016/j.stem.2022.03.004
[2] Lab grown, self-sustainable muscle cells repair muscle injury and disease, mouse study shows. Retrieved Apr 20th ,2022 from https://www.eurekalert.org/news-releases/950288
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