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Updated: Sep 17, 2025
Transplantation of Neonatal Mouse Cardiac Macrophages into Adult Mice
Published on: March 20, 2021
Homotransplantation of Engineered Macrophages with Surface-Modified Nanomedicines for Mitigating Myocardial
Jiahui Cheng1, Rifeng Gao2, Yang Lyu3
1Department of Radiology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong District, Shanghai 200127, China.
Immune disorders are intimately involved in the pathological progression of myocardial ischemia-reperfusion injury (MIRI) and exacerbate cardiac cell damage and mitochondria-related metabolic abnormalities. However, low-immunogenic therapeutic strategies targeting the compromised immune-metabolic microenvironment remain a major challenge. Here, we developed a syngenic reparative macrophage system for the selective delivery of nanoscale drugs by modifying liposomes loaded with nano-Pt/Se and c176 onto the surface of M2 macrophages (PS-c@M). In MIRI mice, transplanted PS-c@M was actively recruited to the myocardial ischemic region, maintained long-lasting residence, and responsively released surface-loaded nanomedicines, which in turn synergistically promoted cardiac cell survival and activated extracellular repair and angiogenesis, thus exerting long-term cardioprotective effects. Specifically, PS-c@M significantly inhibited STING-related signaling pathways, thereby remodeling the immune-inflammatory homeostasis, as evidenced by the increased proportions of M2 macrophages, reparative cardiac resident macrophages, and regulatory T cells and the decreased recruitment and infiltration of M1 macrophages and neutrophils. Moreover, PS-c@M facilitated mitochondrial oxidative phosphorylation and suppressed mitochondria-associated ferroptosis and oxidative damage. This study highlights a low-immunogenic targeted therapeutic strategy based on syngenic reparative macrophages as efficient nanomedicine carriers, with potential for development and application in a wide range of immune and inflammation-related diseases.
Immune disorders are intimately involved in the pathological progression of myocardial ischemia-reperfusion injury (MIRI) and exacerbate cardiac cell damage and mitochondria-related metabolic abnormalities. However, low-immunogenic therapeutic strategies targeting the compromised immune-metabolic microenvironment remain a major challenge. Here, we developed a syngenic reparative macrophage system for the selective delivery of nanoscale drugs by modifying liposomes loaded with nano-Pt/Se and c176 onto the surface of M2 macrophages (PS-c@M). In MIRI mice, transplanted PS-c@M was actively recruited to the myocardial ischemic region, maintained long-lasting residence, and responsively released surface-loaded nanomedicines, which in turn synergistically promoted cardiac cell survival and activated extracellular repair and angiogenesis, thus exerting long-term cardioprotective effects. Specifically, PS-c@M significantly inhibited STING-related signaling pathways, thereby remodeling the immune-inflammatory homeostasis, as evidenced by the increased proportions of M2 macrophages, reparative cardiac resident macrophages, and regulatory T cells and the decreased recruitment and infiltration of M1 macrophages and neutrophils. Moreover, PS-c@M facilitated mitochondrial oxidative phosphorylation and suppressed mitochondria-associated ferroptosis and oxidative damage. This study highlights a low-immunogenic targeted therapeutic strategy based on syngenic reparative macrophages as efficient nanomedicine carriers, with potential for development and application in a wide range of immune and inflammation-related diseases.
