MYOD modified mRNA drives direct on-chip programming of human pluripotent stem cells into skeletal myocytes

Abstract

Drug screening and disease modelling for skeletal muscle related pathologies would strongly benefit from the integration of myogenic cells derived from human pluripotent stem cells within miniaturized cell culture devices, such as microfluidic platform. Here, we identified the optimal culture conditions that allow direct differentiation of human pluripotent stem cells in myogenic cells within microfluidic devices. Myogenic cells are efficiently derived from both human embryonic (hESC) or induced pluripotent stem cells (hiPSC) in eleven days by combining small molecules and non-integrating modified mRNA (mmRNA) encoding for the master myogenic transcription factor MYOD. Our work opens new perspective for the development of patient-specific platforms in which a one-step myogenic differentiation could be used to generate skeletal muscle on-a-chip.