TY - JOUR
T1 - Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells
AU - Baik, June
AU - Ortiz-Cordero, Carolina
AU - Magli, Alessandro
AU - Azzag, Karim
AU - Crist, Sarah B.
AU - Yamashita, Aline
AU - Kiley, James
AU - Selvaraj, Sridhar
AU - Mondragon-Gonzalez, Ricardo
AU - Perrin, Elizabeth
AU - Maufort, John P.
AU - Janecek, Jody L.
AU - Lee, Rachael M.
AU - Stone, Laura Hocum
AU - Rangarajan, Parthasarathy
AU - Ramachandran, Sabarinathan
AU - Graham, Melanie L.
AU - Perlingeiro, Rita C.R.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - RNA sequencing
KW - induced pluripotent stem cells
KW - muscle regeneration
KW - muscular dystrophy
KW - myogenesis
KW - non-human primate
KW - stem cell therapy
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U2 - 10.3390/cells12081147
DO - 10.3390/cells12081147
M3 - Article
C2 - 37190056
AN - SCOPUS:85156169541
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 8
M1 - 1147
ER -