Expansion and Purification Are Critical for the Therapeutic Application of Pluripotent Stem Cell-Derived Myogenic Progenitors.

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Stem cell reports, ISSN: 2213-6711, Vol: 9, Issue: 1, Page: 12-22

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Kim, Jaemin; Magli, Alessandro; Chan, Sunny S K; Oliveira, Vanessa K P; Wu, Jianbo; Darabi, Radbod; Kyba, Michael; Perlingeiro, Rita C R
Elsevier BV
Biochemistry, Genetics and Molecular Biology
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Recent reports have documented the differentiation of human pluripotent stem cells toward the skeletal myogenic lineage using transgene- and cell purification-free approaches. Although these protocols generate myocytes, they have not demonstrated scalability, safety, and in vivo engraftment, which are key aspects for their future clinical application. Here we recapitulate one prominent protocol, and show that it gives rise to a heterogeneous cell population containing myocytes and other cell types. Upon transplantation, the majority of human donor cells could not contribute to myofiber formation. As a proof-of-principle, we incorporated the inducible PAX7 lentiviral system into this protocol, which then enabled scalable expansion of a homogeneous population of skeletal myogenic progenitors capable of forming myofibers in vivo. Our findings demonstrate the methods for scalable expansion of PAX7 myogenic progenitors and their purification are critical for practical application to cell replacement treatment of muscle degenerative diseases.