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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/15/1150 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849770740979597312 |
|---|---|
| author | Zahra Khosrowpour Nivedha Ramaswamy Elise N. Engquist Berkay Dincer Alisha M. Shah Hossam A. N. Soliman Natalya A. Goloviznina Peter I. Karachunski Michael Kyba |
| author_facet | Zahra Khosrowpour Nivedha Ramaswamy Elise N. Engquist Berkay Dincer Alisha M. Shah Hossam A. N. Soliman Natalya A. Goloviznina Peter I. Karachunski Michael Kyba |
| author_sort | Zahra Khosrowpour |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d0746e62748745a385f4163507ef2f2b |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-d0746e62748745a385f4163507ef2f2b2025-08-20T03:02:55ZengMDPI AGCells2073-44092025-07-011415115010.3390/cells14151150Long-Term Engraftment and Satellite Cell Expansion from Human PSC Teratoma-Derived Myogenic ProgenitorsZahra Khosrowpour0Nivedha Ramaswamy1Elise N. Engquist2Berkay Dincer3Alisha M. Shah4Hossam A. N. Soliman5Natalya A. Goloviznina6Peter I. Karachunski7Michael Kyba8Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USAGreg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USASkeletal 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.https://www.mdpi.com/2073-4409/14/15/1150skeletal muscleregenerationteratomatransplantationxenograftsatellite cells |
| spellingShingle | Zahra Khosrowpour Nivedha Ramaswamy Elise N. Engquist Berkay Dincer Alisha M. Shah Hossam A. N. Soliman Natalya A. Goloviznina Peter I. Karachunski Michael Kyba Long-Term Engraftment and Satellite Cell Expansion from Human PSC Teratoma-Derived Myogenic Progenitors Cells skeletal muscle regeneration teratoma transplantation xenograft satellite cells |
| title | Long-Term Engraftment and Satellite Cell Expansion from Human PSC Teratoma-Derived Myogenic Progenitors |
| title_full | Long-Term Engraftment and Satellite Cell Expansion from Human PSC Teratoma-Derived Myogenic Progenitors |
| title_fullStr | Long-Term Engraftment and Satellite Cell Expansion from Human PSC Teratoma-Derived Myogenic Progenitors |
| title_full_unstemmed | Long-Term Engraftment and Satellite Cell Expansion from Human PSC Teratoma-Derived Myogenic Progenitors |
| title_short | Long-Term Engraftment and Satellite Cell Expansion from Human PSC Teratoma-Derived Myogenic Progenitors |
| title_sort | long term engraftment and satellite cell expansion from human psc teratoma derived myogenic progenitors |
| topic | skeletal muscle regeneration teratoma transplantation xenograft satellite cells |
| url | https://www.mdpi.com/2073-4409/14/15/1150 |
| work_keys_str_mv | AT zahrakhosrowpour longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors AT nivedharamaswamy longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors AT elisenengquist longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors AT berkaydincer longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors AT alishamshah longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors AT hossamansoliman longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors AT natalyaagoloviznina longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors AT peterikarachunski longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors AT michaelkyba longtermengraftmentandsatellitecellexpansionfromhumanpscteratomaderivedmyogenicprogenitors |