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

Pharmaceutics. 2023 Jul 6;15(7):1897. doi: 10.3390/pharmaceutics15071897.

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: 3D gastruloids; budesonide analogues; drug toxicity; pluripotency exit; stem cells.