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Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling

Choi, SungWoo; Ferrari, Giulia; Moyle, Louise A; Mackinlay, Kirsty; Naouar, Naira; Jalal, Salma; Benedetti, Sara; ... Tedesco, Francesco Saverio; + view all (2022) Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling. EMBO Molecular Medicine , 2022 , Article e14526. 10.15252/emmm.202114526. (In press). Green open access

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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.

Type: Article
Title: Assessing and enhancing migration of human myogenic progenitors using directed iPS cell differentiation and advanced tissue modelling
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/emmm.202114526
Publisher version: https://doi.org/10.15252/emmm.202114526
Language: English
Additional information: © 2022 The Authors. Published under the terms of the CC BY 4.0 license.
Keywords: cell migration, cell therapy, iPS cells, muscular dystrophy, tissue engineering
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10156566
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