Three-dimensional culture systems reverse cellular aging in limbal niche cells through activation of FOSL1, a transcription factor that preserves mitochondrial function and reduces oxidative stress. This finding addresses a critical barrier to clinical stem cell therapies for corneal regeneration, where conventional culture methods accelerate cellular aging during expansion.
Key Points
- 3D culture restores stemness and proliferative capacity versus 2D methods
- FOSL1 upregulation protects mitochondrial integrity and reduces ROS production
- FOSL1 manipulation directly controls aging trajectory in cultured cells
Longevity Analysis
Cellular aging during laboratory expansion has limited the clinical application of regenerative stem cell therapies. This research demonstrates that physical microenvironment—specifically three-dimensional structure—can reverse senescence at the molecular level by preserving the energy-producing capacity of cells and their ability to manage oxidative stress. The mechanism involves a single transcription factor that coordinates both metabolic resilience and proliferative signaling. For therapeutic translation, this suggests that optimizing culture conditions before clinical deployment could restore cellular function that would otherwise deteriorate in aging tissues, extending the therapeutic window for degenerative conditions affecting tissues with high turnover rates.
Original published by Wiley Aging Cell, by Xuying Wang, Shen Li, Zibin Liu, Xinghan Guo, Jiachao Shen, Tianyu Zhou, Shuying Liao, Xiaoyu Huang, Wei Wang, Lingjuan Xu, Xinjie Zang, Guigang Li .