DOI: 10.1126/sciadv.aef8069 ISSN: 2375-2548
Photosynthetic chimeric stem cells function as mitochondrial batteries
Zhengtai Chen, Hanxiao Sun, Yuanyang Zheng, Xuan Jiang, Yan He, Kai Ye, Yufan Zhang, Zhengwei Mao, Ziyi Zhou, Xiaoxi Lin, Chenggang Yi, Wei Wang
Therapies built on mitochondrial transfer hold promise for repairing dysfunctional, energy-deficient cells. Still, mesenchymal stem cells used as mitochondrial donors are limited by poor engraftment, risk of aberrant differentiation, and low transfer efficiency. Herein, we constructed photosynthesis-empowered cross-kingdom chimeric stem cells (PCSs; “mitochondrial battery”) by introducing plant-derived thylakoid-based artificial nuclei plus
FGF21
-encoding messenger RNA (mRNA) into enucleated bone marrow mesenchymal stem cells. Photosynthetic activity enhances mitochondrial transfer to restore metabolism in damaged cells and elevates anabolism to increase FGF21 production. Sustained FGF21 release promotes mitochondrial biogenesis and sustains long-term cellular energy homeostasis. Mouse and porcine wound healing models demonstrate that PCSs recharge cellular energy to accelerate wound repair. This light-activated cellular photosynthetic platform supports modular mRNA programmability, shows no engraftment or aberrant differentiation, and allows repeated administration for diverse therapeutic applications.