Abstract
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.
Funding Information
  • National Natural Science Foundation of China (82272296)
  • National Natural Science Foundation of China (82472552)
  • National Natural Science Foundation of China (32371404)
  • Medical-Engineering Cross Foundation of Shanghai Jiao Tong University (YG2026QNA43)
  • Zhejiang University School of Medicine Affiliated Second Hospital start-up funds (Y199532022)
  • Specialized disease cohort project (2025DLB01)

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