Budesonide Analogues Preserve Stem Cell Pluripotency and Delay 3D Gastruloid Development

Abstract

Small molecules that can modulate or stabilize cell–cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as an anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.

Keywords

• drug toxicity
• budesonide analogues
• stem cells
• pluripotency exit
• 3D gastruloids