Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells
Pluripotent stem (PS) cells enable the scalable production of tissue-specific derivatives with therapeutic potential for various clinical applications, including muscular dystrophies. Given the similarity to human counterparts, the non-human primate (NHP) is an ideal preclinical model to evaluate se...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/8/1147 |
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| author | June Baik Carolina Ortiz-Cordero Alessandro Magli Karim Azzag Sarah B. Crist Aline Yamashita James Kiley Sridhar Selvaraj Ricardo Mondragon-Gonzalez Elizabeth Perrin John P. Maufort Jody L. Janecek Rachael M. Lee Laura Hocum Stone Parthasarathy Rangarajan Sabarinathan Ramachandran Melanie L. Graham Rita C. R. Perlingeiro |
| author_facet | June Baik Carolina Ortiz-Cordero Alessandro Magli Karim Azzag Sarah B. Crist Aline Yamashita James Kiley Sridhar Selvaraj Ricardo Mondragon-Gonzalez Elizabeth Perrin John P. Maufort Jody L. Janecek Rachael M. Lee Laura Hocum Stone Parthasarathy Rangarajan Sabarinathan Ramachandran Melanie L. Graham Rita C. R. Perlingeiro |
| author_sort | June Baik |
| collection | DOAJ |
| description | Pluripotent stem (PS) cells enable the scalable production of tissue-specific derivatives with therapeutic potential for various clinical applications, including muscular dystrophies. Given the similarity to human counterparts, the non-human primate (NHP) is an ideal preclinical model to evaluate several questions, including delivery, biodistribution, and immune response. While the generation of human-induced PS (iPS)-cell-derived myogenic progenitors is well established, there have been no data for NHP counterparts, probably due to the lack of an efficient system to differentiate NHP iPS cells towards the skeletal muscle lineage. Here, we report the generation of three independent Macaca fascicularis iPS cell lines and their myogenic differentiation using PAX7 conditional expression. The whole-transcriptome analysis confirmed the successful sequential induction of mesoderm, paraxial mesoderm, and myogenic lineages. NHP myogenic progenitors efficiently gave rise to myotubes under appropriate in vitro differentiation conditions and engrafted in vivo into the TA muscles of NSG and FKRP-NSG mice. Lastly, we explored the preclinical potential of these NHP myogenic progenitors in a single wild-type NHP recipient, demonstrating engraftment and characterizing the interaction with the host immune response. These studies establish an NHP model system through which iPS-cell-derived myogenic progenitors can be studied. |
| first_indexed | 2024-03-11T05:09:29Z |
| format | Article |
| id | doaj.art-ca90a32d1b4844d29800015a149982ef |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:09:29Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ca90a32d1b4844d29800015a149982ef2023-11-17T18:43:10ZengMDPI AGCells2073-44092023-04-01128114710.3390/cells12081147Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem CellsJune Baik0Carolina Ortiz-Cordero1Alessandro Magli2Karim Azzag3Sarah B. Crist4Aline Yamashita5James Kiley6Sridhar Selvaraj7Ricardo Mondragon-Gonzalez8Elizabeth Perrin9John P. Maufort10Jody L. Janecek11Rachael M. Lee12Laura Hocum Stone13Parthasarathy Rangarajan14Sabarinathan Ramachandran15Melanie L. Graham16Rita C. R. Perlingeiro17Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USAStem Cell Resources and the Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USAStem Cell Resources and the Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USADepartment of Surgery, University of Minnesota, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USAPluripotent stem (PS) cells enable the scalable production of tissue-specific derivatives with therapeutic potential for various clinical applications, including muscular dystrophies. Given the similarity to human counterparts, the non-human primate (NHP) is an ideal preclinical model to evaluate several questions, including delivery, biodistribution, and immune response. While the generation of human-induced PS (iPS)-cell-derived myogenic progenitors is well established, there have been no data for NHP counterparts, probably due to the lack of an efficient system to differentiate NHP iPS cells towards the skeletal muscle lineage. Here, we report the generation of three independent Macaca fascicularis iPS cell lines and their myogenic differentiation using PAX7 conditional expression. The whole-transcriptome analysis confirmed the successful sequential induction of mesoderm, paraxial mesoderm, and myogenic lineages. NHP myogenic progenitors efficiently gave rise to myotubes under appropriate in vitro differentiation conditions and engrafted in vivo into the TA muscles of NSG and FKRP-NSG mice. Lastly, we explored the preclinical potential of these NHP myogenic progenitors in a single wild-type NHP recipient, demonstrating engraftment and characterizing the interaction with the host immune response. These studies establish an NHP model system through which iPS-cell-derived myogenic progenitors can be studied.https://www.mdpi.com/2073-4409/12/8/1147non-human primateinduced pluripotent stem cellsmyogenesisRNA sequencingmuscle regenerationmuscular dystrophy |
| spellingShingle | June Baik Carolina Ortiz-Cordero Alessandro Magli Karim Azzag Sarah B. Crist Aline Yamashita James Kiley Sridhar Selvaraj Ricardo Mondragon-Gonzalez Elizabeth Perrin John P. Maufort Jody L. Janecek Rachael M. Lee Laura Hocum Stone Parthasarathy Rangarajan Sabarinathan Ramachandran Melanie L. Graham Rita C. R. Perlingeiro Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells Cells non-human primate induced pluripotent stem cells myogenesis RNA sequencing muscle regeneration muscular dystrophy |
| title | Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells |
| title_full | Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells |
| title_fullStr | Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells |
| title_full_unstemmed | Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells |
| title_short | Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells |
| title_sort | establishment of skeletal myogenic progenitors from non human primate induced pluripotent stem cells |
| topic | non-human primate induced pluripotent stem cells myogenesis RNA sequencing muscle regeneration muscular dystrophy |
| url | https://www.mdpi.com/2073-4409/12/8/1147 |
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