Mitochondrial dysfunction is common in macrophages with impaired efferocytosis, and this dysfunction can hinder the recovery from tissue damage. Targeting intercellular mitochondrial transfer is a promising strategy to enhance the potential of cell therapy. This study elucidates the stress-resistant capabilities of anucleate platelet mitochondria and demonstrates that platelets can transfer mitochondria to macrophages under cellular stress, thereby restoring their impaired efferocytotic function. In this study, a delivery system was designed:Cationic polymer nanoparticles (NPs) carrying a load were used to couple platelets overexpressing PPARγ with macrophages (M-P-NPs@PPARγ). In this system, activated platelets can induce mitochondrial transfer and release the NPs into macrophages, thereby enhancing ATP production and maintaining lipid homeostasis. This concept was validated using a representative central nervous system disease with defective efferocytosis—the spinal cord injury model.It has been demonstrated that M-P-NP@PPARγ can reverse impaired phagocytosis, thereby promoting nerve regeneration and myelin repair, ultimately facilitating the recovery of motor function. In summary, this study developed a strategy that combines mitochondrial and gene delivery to restore the phagocytic function of macrophages after injury by regulating energy and lipid metabolism.

Original link

Advanced Science ( IF 14.1 )

Pub Date : 2025-12-25

DOI: 10.1002/advs.202513474

Haoli Wang,  Hao Hu,  Yijun Li,  Lintao Hu,  Chenhui Gu,  Yiwei Zhu,  Jing Huang,  Na Li,  Shuqi Jiang,  Shouyan Zu,  Jiachen Xu,  Yining Wang,  Ke Yang,  Pengfei Chen,  Liqing Shangguan,  Yongcheng Wang,  Shunwu Fan,  Xianfeng Lin,  Qingqing Wang