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Updated: Jun 6, 2025
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Graft-derived extracellular vesicles transport miRNAs to modulate macrophage polarization after heart transplantation
Lei Zheng1, Shuling Han2, Jeanna Enriquez2
1Transplant Immunology Lab, Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA; Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai, China.
Heart transplantation, a crucial intervention for saving lives of those with end-stage cardiac failure, often faces complications from acute allograft rejection. This study focuses on the intricate dynamics of immune cell interactions and specific communication pathways between organs, which are not yet well understood. Our study investigates this interplay using a murine heterotopic transplant model, using single-cell RNA sequencing to examine CD45+ immune cells from both the heart grafts and spleens. We conduct a comprehensive analysis focused on functional enrichment, cell trajectory, and interorgan communication in heart transplants, highlighting dynamic interactions between monocyte/macrophage subtypes that is mediated by extracellular vesicles (EVs). We use unsupervised clustering and elucidate the complex cellular interactions that influence allograft outcomes. Notably, we discovered that microRNA-363 and microRNA-709, carried by EVs from CD63+ graft macrophages, can induce M1 polarization within the recipient's spleen via the Fcho2/Notch1 signaling pathway. These insights illuminate the nuanced immune responses during acute cardiac rejection and suggest that targeting EVs from graft-resident macrophages may offer a new strategy to mitigate transplant rejection.
Heart transplantation, a crucial intervention for saving lives of those with end-stage cardiac failure, often faces complications from acute allograft rejection. This study focuses on the intricate dynamics of immune cell interactions and specific communication pathways between organs, which are not yet well understood. Our study investigates this interplay using a murine heterotopic transplant model, using single-cell RNA sequencing to examine CD45+ immune cells from both the heart grafts and spleens. We conduct a comprehensive analysis focused on functional enrichment, cell trajectory, and interorgan communication in heart transplants, highlighting dynamic interactions between monocyte/macrophage subtypes that is mediated by extracellular vesicles (EVs). We use unsupervised clustering and elucidate the complex cellular interactions that influence allograft outcomes. Notably, we discovered that microRNA-363 and microRNA-709, carried by EVs from CD63+ graft macrophages, can induce M1 polarization within the recipient's spleen via the Fcho2/Notch1 signaling pathway. These insights illuminate the nuanced immune responses during acute cardiac rejection and suggest that targeting EVs from graft-resident macrophages may offer a new strategy to mitigate transplant rejection.
