Glycogen engineering improves the starvation resistance of mesenchymal stem cells and their therapeutic efficacy in pulmonary fibrosis
Year: 2025
Type: preprint
Abstract: Mesenchymal stem cells (MSCs) are widely used in regenerative medicine, including the treatment of pulmonary fibrosis. However, implanted MSCs disappear within days, constraining therapeutic efficacy, which is largely attributed to nutrient deprivation. In this study, we established glycogen metabolism engineering strategies in mammalian cells. By expressing a functionally optimized glycogen synthase (GYSmut), MSCs could accumulate large amounts of glycogen rapidly as a reserve substance. Glycogen engineering significantly improved the survival of MSCs during starvation both in vitro and in vivo, enhancing cell viability post-implantation and their therapeutic efficacy in pulmonary fibrosis. Glycogen-engineered MSCs may serve as chassis cells for further applications. Our research highlights the importance of glucose metabolism regulation in cell-based therapy and demonstrates the great potential for the metabolic engineering of MSCs and other therapeutic cells.
Source: eLife
DOI: 10.7554/elife.106023
Authors: Yongyue Xu, Mamatali Rahman, Zhaoyan Wang, Bo Zhang, Hanqi Xie, Lei Wang, Haowei Xu, Xiaodan Sun, Shan Cheng, Qiong Wu
Institutions: Tsinghua University, Capital Medical University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Award: G3205759590
OpenAlex ID: W4411370665