Great Ormond Street Institute of Child Health, University College London, WC1N1EH, London, UK.
Venetian Institute of Molecular Medicine (VIMM), 35129, Padova, Italy; Industrial Engineering Department, University of Padova, 35131, Padova, Italy.
Biochem Biophys Res Commun. 2021 Jun 30;560:139-145. doi: 10.1016/j.bbrc.2021.04.129. Epub 2021 May 11.
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.
药物筛选和骨骼肌肉相关疾病模型的建立将从人类多能干细胞衍生的成肌细胞与微流控芯片等小型化细胞培养设备的整合中获益匪浅。在这里，我们确定了最佳的培养条件，使人类多能干细胞可以在微流控设备内直接分化为成肌细胞。通过结合小分子和编码主成肌转录因子 MYOD 的非整合修饰信使 RNA（mmRNA），可以在 11 天内从人类胚胎干细胞（hESC）或诱导多能干细胞（hiPSC）中有效地获得成肌细胞。我们的工作为开发患者特异性平台开辟了新的视角，其中一步法成肌分化可用于在芯片上生成骨骼肌。
