EAGER: Biomanufacturing: Controlling stem cell behavior via novel photo activation of FGF signaling pathway using blue light

PI：Lee，Gabsang提案编号：1547515干细胞生物学的最新进展在再生医学中具有巨大潜力。为了实现干细胞的治疗前景，实现高质量和高精度培养系统的方法是必不可少的。研究人员提出了一种创新的方法，通过蓝光照明来光学控制干细胞的行为。如果成功，该方法将通过控制多种信号通路扩展到其他干细胞应用。目前的干细胞培养系统包括不同的生长因子，但它们在培养基中的不均匀分布（缺乏空间控制），以及由于时间不稳定性而逐渐降低的活性，通常在大规模干细胞生物制造中引起显著的问题。为了解决这一问题，研究人员提出了光诱导调节人多能干细胞和肌肉干细胞中的成纤维细胞生长因子（FGF）信号，使用创新的光学控制成纤维细胞生长因子受体（OptoFGFR）系统，允许精确控制FGF信号。该研究将加速干细胞的体外和体内时空调制，并将成为具有潜在翻译特性的干细胞生物学中“光信号”应用的第一个例子。更重要的是，OptoFGFR系统将扩展到其他信号通路，如表皮生长因子（EGF），血管内皮生长因子VEGF和神经生长因子（NGF），如果成功，该方法可能对多种人类疾病有用。

PI: Lee, Gabsang Proposal Number: 1547515 Recent advances in stem cell biology hold great potential in regenerative medicine. To realize the therapeutic promise of stem cells, approach to realize high-quality and high-precision culture system is essential. The investigator proposes an innovative approach of optical control of stem cell behaviors through blue light illumination. If successful the approach will be expanded to other stem cell applications by controlling multiple signaling pathways. Current stem cell culture systems include different growth factors, but their uneven distribution in the media (lack of spatial control), and gradually decreased activity due to temporal-instability, often cause significant problems in a large-scale stem cell biomanufacturing. To address this problem, the investigator proposes photo-inducible modulation of fibroblast growth factor (FGF) signaling in human pluripotent stem cells and muscle stem cells, using an innovative optically controlled fibrobast growth factor receptor (OptoFGFR) system allowing precise control of FGF signaling. The proposed investigation will accelerate the in vitro and in vivo spatio-temporal modulation of stem cells, and will be the first example of the 'opto-signaling' application in stem cell biology with potential translational characteristics. More importantly, the OptoFGFR system will be expanded to other signaling pathways such as epidermal growth factor (EGF), vascular endothelial growth factor VEGF, and nerve growth factor (NGF), and if successful the approach could be useful for multiple human diseases.