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

• DOI: 10.20944/preprints202305.2155.v1
• Publication Date: 2023-05-31T05:33:27Z
• Authors: Filomena Amoroso; Eduardo Ibello; Federica Saracino; Federica Cermola; Giovanna Ponticelli; Enrica Scalera; Francesca Ricci; Gino Villetti; Gilda Cobellis; Gabriella Minchiotti; Eduardo Jorge Pat...; Dario De Cesare; Cristina D'Aniello
• Keywords: 0301 basic medicine; pluripotency exit; 3D gastruloids; budesonide analogues; drug toxicity; pluripotency exit; stem cells; 3D gastruloids; drug toxicity; Article; 3. Good health; RS1-441; 03 medical and health sciences; Pharmacy and materia medica; stem cells; drug toxicity; budesonide analogues; stem cells; pluripotency exit; 3D gastruloids; budesonide analogues

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 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.