1. Producing Engraftable Skeletal Myogenic Progenitors from Pluripotent Stem Cells via Teratoma Formation.
- Author
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Xie N and Chan SSK
- Subjects
- Mice, Animals, Muscle Fibers, Skeletal metabolism, Cell Differentiation, Intercellular Signaling Peptides and Proteins, Muscle, Skeletal metabolism, Muscle Development, Pluripotent Stem Cells, Satellite Cells, Skeletal Muscle metabolism, Teratoma etiology
- Abstract
Generating engraftable skeletal muscle progenitor cells is a promising cell therapy approach to treating degenerating muscle diseases. Pluripotent stem cell (PSC) is an ideal cell source for cell therapy because of its unlimited proliferative capability and potential to differentiate into multiple lineages. Approaches such as ectopic overexpression of myogenic transcription factors and growth factors-directed monolayer differentiation, while able to differentiate PSCs into the skeletal myogenic lineage in vitro, are limited in producing muscle cells that reliably engraft upon transplantation. Here we present a novel method to differentiate mouse PSCs into skeletal myogenic progenitors without genetic modification or monolayer culture. We make use of forming a teratoma, in which skeletal myogenic progenitors can be routinely obtained. We first inject mouse PSCs into the limb muscle of an immuno-compromised mouse. Within 3-4 weeks, α7-integrin+ VCAM-1+ skeletal myogenic progenitors are purified by fluorescent-activated cell sorting. We further transplant these teratoma-derived skeletal myogenic progenitors into dystrophin-deficient mice to assess engraftment efficiency. This teratoma formation strategy is capable of generating skeletal myogenic progenitors with high regenerative potency from PSCs without genetic modifications or growth factors supplementation., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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