Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling
Abstract Muscle satellite stem cells (MuSCs) are responsible for skeletal muscle growth and regeneration. Despite their differentiation potential, human MuSCs have limited in vitro expansion and in vivo migration capacity, limiting their use in cell therapies for diseases affecting multiple skeletal...
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-09-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202114526 |
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| author | SungWoo Choi Giulia Ferrari Louise A Moyle Kirsty Mackinlay Naira Naouar Salma Jalal Sara Benedetti Christine Wells Francesco Muntoni Francesco Saverio Tedesco |
| author_facet | SungWoo Choi Giulia Ferrari Louise A Moyle Kirsty Mackinlay Naira Naouar Salma Jalal Sara Benedetti Christine Wells Francesco Muntoni Francesco Saverio Tedesco |
| author_sort | SungWoo Choi |
| collection | DOAJ |
| description | Abstract Muscle satellite stem cells (MuSCs) are responsible for skeletal muscle growth and regeneration. Despite their differentiation potential, human MuSCs have limited in vitro expansion and in vivo migration capacity, limiting their use in cell therapies for diseases affecting multiple skeletal muscles. Several protocols have been developed to derive MuSC‐like progenitors from human induced pluripotent stem (iPS) cells (hiPSCs) to establish a source of myogenic cells with controllable proliferation and differentiation. However, current hiPSC myogenic derivatives also suffer from limitations of cell migration, ultimately delaying their clinical translation. Here we use a multi‐disciplinary approach including bioinformatics and tissue engineering to show that DLL4 and PDGF‐BB improve migration of hiPSC‐derived myogenic progenitors. Transcriptomic analyses demonstrate that this property is conserved across species and multiple hiPSC lines, consistent with results from single cell motility profiling. Treated cells showed enhanced trans‐endothelial migration in transwell assays. Finally, increased motility was detected in a novel humanised assay to study cell migration using 3D artificial muscles, harnessing advanced tissue modelling to move hiPSCs closer to future muscle gene and cell therapies. |
| format | Article |
| id | doaj-art-d97ee7a0ff1642abb21d74e59559ab3d |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2022-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-d97ee7a0ff1642abb21d74e59559ab3d2025-08-20T03:46:13ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-09-01141011910.15252/emmm.202114526Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modellingSungWoo Choi0Giulia Ferrari1Louise A Moyle2Kirsty Mackinlay3Naira Naouar4Salma Jalal5Sara Benedetti6Christine Wells7Francesco Muntoni8Francesco Saverio Tedesco9The Francis Crick InstituteDepartment of Cell and Developmental Biology, University College LondonDepartment of Cell and Developmental Biology, University College LondonDepartment of Cell and Developmental Biology, University College LondonInstitut de Biologie Paris Seine FR3631, Plateforme de Bioinformatique ARTbio, Sorbonne UniversitéThe Francis Crick InstituteUCL Great Ormond Street Institute of Child Health, University College LondonCentre for Stem Cell Systems, The University of MelbourneNational Institute for Health Research Great Ormond Street Hospital Biomedical Research CentreThe Francis Crick InstituteAbstract Muscle satellite stem cells (MuSCs) are responsible for skeletal muscle growth and regeneration. Despite their differentiation potential, human MuSCs have limited in vitro expansion and in vivo migration capacity, limiting their use in cell therapies for diseases affecting multiple skeletal muscles. Several protocols have been developed to derive MuSC‐like progenitors from human induced pluripotent stem (iPS) cells (hiPSCs) to establish a source of myogenic cells with controllable proliferation and differentiation. However, current hiPSC myogenic derivatives also suffer from limitations of cell migration, ultimately delaying their clinical translation. Here we use a multi‐disciplinary approach including bioinformatics and tissue engineering to show that DLL4 and PDGF‐BB improve migration of hiPSC‐derived myogenic progenitors. Transcriptomic analyses demonstrate that this property is conserved across species and multiple hiPSC lines, consistent with results from single cell motility profiling. Treated cells showed enhanced trans‐endothelial migration in transwell assays. Finally, increased motility was detected in a novel humanised assay to study cell migration using 3D artificial muscles, harnessing advanced tissue modelling to move hiPSCs closer to future muscle gene and cell therapies.https://doi.org/10.15252/emmm.202114526cell migrationcell therapyiPS cellsmuscular dystrophytissue engineering |
| spellingShingle | SungWoo Choi Giulia Ferrari Louise A Moyle Kirsty Mackinlay Naira Naouar Salma Jalal Sara Benedetti Christine Wells Francesco Muntoni Francesco Saverio Tedesco Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling EMBO Molecular Medicine cell migration cell therapy iPS cells muscular dystrophy tissue engineering |
| title | Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling |
| title_full | Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling |
| title_fullStr | Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling |
| title_full_unstemmed | Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling |
| title_short | Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling |
| title_sort | assessing and enhancing migration of human myogenic progenitors using directed ips cell differentiation and advanced tissue modelling |
| topic | cell migration cell therapy iPS cells muscular dystrophy tissue engineering |
| url | https://doi.org/10.15252/emmm.202114526 |
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