Lyophilized platelet derived extracellular vesicles promote hemostasis and attenuate intracranial hemorrhage following traumatic brain injury.

Authors

Alpa Trivedi, Byron Miyazawa, Alexander T Fields, Michael Matthews, Lindsay Vivona, Callie Keane, Daniel Potter, Huimin Geng, Haoqian Zhang, Hiroki Taenaka, Serena S Kwek, Kimberly Herrera-Rodriguez, Brenda Nunez-Garcia, Erika Marques de Menezes, Mark Barry, Alison Nair, Ben Kuhn, Philip J Norris, Lawrence Fong, Michael M Fitzpatrick, Martin Schreiber, Lucy Z Kornblith, Shibani Pati

Published in

Journal of translational medicine. Jul 20, 2026. Epub Jul 20, 2026.

Abstract

Hemorrhage is the leading cause of preventable death world-wide. Traumatic brain injury (TBI) is the primary driver of mortality and morbidity among individuals aged 1-44 years worldwide, with intracranial hemorrhage (ICH) being the major contributor to acute mortality post-TBI. Based on prior studies, we hypothesized that lyophilized platelet-derived extracellular vesicles (LPEVs) would reduce ICH and preserve blood-brain barrier (BBB) integrity after TBI.
LPEVs were characterized by flow cytometry, scanning electron microscopy, and Nanosight. LPEVs were evaluated in vitro in human brain endothelial cell monolayers for barrier integrity. Utilizing a murine TBI model of controlled cortical impact, LPEVs were transfused 40 min after injury. The degree of BBB permeability was quantitated by 10kD infrared-tagged dye that leakage into the brain. ICH was quantitated by RBCs using Ter-119 antibody. Murine tail snip and cremaster muscle vascular injury models and thromboelastography analysis of healthy donor or trauma patient blood were used to assess hemostatic ability of LPEVs. Proteomic content was analyzed by mass spectrometry and mRNA and miRNA content by next-generation sequencing. Light transmission aggregometry using fresh apheresis platelets or generated dysfunctional platelets supported the mechanistic pathway assessment.
LPEVs were predominantly in the exosome range, expressed platelet and microvesicle markers and generated thrombin. In vitro, LPEVs attenuated thrombin-induced paracellular permeability and reduced intercellular gaps in human brain microvascular endothelial cells. In vivo, LPEVs exhibited potent hemostatic activity in a murine tail-transection and cremaster vascular injury models. Following experimental TBI in mice, acute administration of LPEVs significantly reduced ICH without impacting BBB permeability. Multi-omics analyses revealed that LPEVs retained platelet-derived hemostatic cargo, but lacked the vasculoprotective factors, typically present in intact platelets. LPEVs accelerated clot formation in blood from healthy donors, trauma patients, and dysfunctional platelet preparations. Mechanistically, LPEVs promote hemostasis in part through GPIIb/IIIa-dependent platelet aggregation.
These data demonstrate the therapeutic and hemostatic efficacy of LPEVs in reducing ICH following TBI without affecting BBB permeability or neuroinflammation. The multi-omics and GPIIB/IIIA driven data can potentially explain the decoupled effects of LPEVs on hemostasis and vascular permeability in our experimental TBI model.

PMID:
42472813
Bibliographic data and abstract were imported from PubMed on 20 Jul 2026.

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