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CD63 aptamer–based electrochemical sensor assesses stored red blood cell–derived exosome burden associated with mast-cell–mediated transfusion-related acute lung injury
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DOI：10.1186/s12951-026-04917-x.png)
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Abstract
En 中文
Transfusion-related acute lung injury (TRALI) remains a serious complication of transfusion, and blood component–derived exosomes have been proposed as candidate contributors to transfusion-related inflammatory dysregulation. Rapid and practical methods to assess exosome burden in stored red blood cell (RBC) units remain limited. Here, we developed a CD63 electrochemical aptamer-based (E-AB) sensor as a preliminary analytical platform to rapidly detect exosome-associated signals and investigated whether stored red-blood-cell–derived exosomes (EXs-RBC) contribute to mast-cell–associated inflammatory lung injury in TRALI-relevant models. Using the CD63 E-AB sensor, we assessed EXs-RBC signals in stored RBC units, isolated EXs-RBC for HMC-1 cell stimulation and mouse experiments, and evaluated their inflammatory effects. The CD63 E-AB readout decreased in a concentration-dependent manner with increasing exosome levels. EXs-RBC dose-dependently amplified inflammatory responses, and these effects were attenuated by pharmacologic mast-cell inhibition or mast-cell deficiency. In antibody-independent TRALI-relevant inflammatory lung injury models and a supportive antibody-mediated TRALI-like model, EXs-RBC exacerbated lung injury and were associated with activation of the mast-cell toll-like receptor 3 (TLR3)–mitogen-activated protein kinase (MAPK) signaling. Collectively, these findings support the feasibility of using a CD63 E-AB sensor to assess exosome burden in stored RBC units and provide experimental evidence that EXs-RBC can amplify mast-cell-associated inflammatory lung injury in TRALI-relevant models, supporting further investigation of EXs-RBC burden as a candidate donor-side metric in transfusion safety research.
Keywords:
Exosomes
Electrochemical aptamer-based sensors
Mast cells
Rapid detection
Transfusion-related acute lung injury
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