Abstract:
Research into Schwann cell (SC)-related diseases has been hampered by the difficulty of obtaining human-derived SCs, which have limited proliferative capacity. This has resulted in a delay in progress in drug discovery and cell therapy targeting SCs. To overcome these limitations, we developed a robust method for inducing the differentiation of human induced pluripotent stem cells (hiPSCs) into SCs. We established hiPSC lines and successfully generated high-purity Schwann cell precursors (SCPs) from size-controlled hiPSC aggregates by precisely timed treatment with our proprietary enzyme solution. Such SCPs were successfully expanded and further differentiated into myelin basic protein (MBP) expressing SC populations when treated with an appropriate medium containing dibutyryl-cAMP (db-cAMP). These differentiated cells secreted factors that induced neurite outgrowth in vitro. Our method allows for the efficient and stable production of SCPs and SCs from hiPSCs. This robust induction and maturation method has the potential to be a valuable tool in drug discovery and cell therapy targeting SC-related diseases.
摘要:
对雪旺氏细胞(SC)相关疾病的研究因难以获得人类来源的SC而受到阻碍,具有有限的增殖能力。这导致药物发现和靶向SC的细胞疗法的进展延迟。为了克服这些限制,我们开发了一种诱导人诱导多能干细胞(hiPSCs)分化为SCs的强大方法。我们建立了hiPSC细胞系,并通过使用我们专有的酶溶液进行精确定时处理,从大小控制的hiPSC聚集体中成功生成了高纯度的施万细胞前体(SCP)。当用含有二丁酰-cAMP(db-cAMP)的适当培养基处理时,这种SCP成功扩增并进一步分化为表达髓磷脂碱性蛋白(MBP)的SC群体。这些分化的细胞分泌在体外诱导神经突生长的因子。我们的方法允许从hiPSC有效且稳定地生产SCP和SC。这种强大的诱导和成熟方法有可能成为靶向SC相关疾病的药物发现和细胞治疗的有价值的工具。