Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells
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cells-12-01147-v2.pdf
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2.78 MB
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Author(s)
Baik, June
Ortiz-Cordero, Carolina
Magli, Alessandro
Azzag, Karim
Crist, Sarah B.
Yamashita, Aline
Kiley, James
Selvaraj, Sridhar
Mondragon-Gonzalez, Ricardo
Perrin, Elizabeth
Date Issued
April 13, 2023
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Cells 12 (8): 1147 (2023)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.3390/cells12081147
