Long-Term Engraftment and Satellite Cell Expansion from Human PSC Teratoma-Derived Myogenic Progenitors

Skeletal muscle regeneration requires a reliable source of myogenic progenitor cells capable of forming new fibers and creating a self-renewing satellite cell pool. Human induced pluripotent stem cell (hiPSC)-derived teratomas have emerged as a novel in vivo platform for generating skeletal myogenic...

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Main Authors: Zahra Khosrowpour, Nivedha Ramaswamy, Elise N. Engquist, Berkay Dincer, Alisha M. Shah, Hossam A. N. Soliman, Natalya A. Goloviznina, Peter I. Karachunski, Michael Kyba
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/15/1150
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Summary:Skeletal muscle regeneration requires a reliable source of myogenic progenitor cells capable of forming new fibers and creating a self-renewing satellite cell pool. Human induced pluripotent stem cell (hiPSC)-derived teratomas have emerged as a novel in vivo platform for generating skeletal myogenic progenitors, although in vivo studies to date have provided only an early single-time-point snapshot. In this study, we isolated a specific population of CD82<sup>+</sup> ERBB3<sup>+</sup> NGFR<sup>+</sup> cells from human iPSC-derived teratomas and verified their long-term in vivo regenerative capacity following transplantation into NSG-mdx<sup>4Cv</sup> mice. Transplanted cells engrafted, expanded, and generated human Dystrophin<sup>+</sup> muscle fibers that increased in size over time and persisted stably long-term. A dynamic population of PAX7<sup>+</sup> human satellite cells was established, initially expanding post-transplantation and declining moderately between 4 and 8 months as fibers matured. MyHC isoform analysis revealed a time-based shift from embryonic to neonatal and slow fiber types, indicating a slow progressive maturation of the graft. We further show that these progenitors can be cryopreserved and maintain their engraftment potential. Together, these findings give insight into the evolution of teratoma-derived human myogenic stem cell grafts, and highlight the long-term regenerative potential of teratoma-derived human skeletal myogenic progenitors.
ISSN:2073-4409