Donor Sex and Platelet Storage Change the Therapeutic Effects of Platelet-Derived Extracellular Vesicles on Endothelium

Authors

• Mandeep Kaur
• Malvika Gupta
• Sowmya Shree Gopal
• Charles E Wade
• Jessica C Cardenas
• Amit K Srivastava

Language

English

Publication Date

5-1-2026

Journal

Blood Vessels, Thrombosis & Hemostasis

DOI

10.1016/j.bvth.2026.100148

PMID

41938043

PMCID

PMC13050065

PubMedCentral® Posted Date

2-16-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Platelet-derived extracellular vesicles (PEVs) play an active role in vascular protection and repair and are being explored as a viable alternative to platelet therapy. Because platelet function and stability are shaped by donor sex and storage conditions, these same factors are likely to influence the PEVs they release. Understanding these influences is key to developing PEVs into a safe and dependable therapeutic option. In this study, we investigated how donor sex and platelet storage affect the therapeutic properties of PEVs. To address this, PEVs were isolated from platelets of healthy male and female donors. Platelets were either processed immediately after blood collection to represent a resting state or stored overnight at room temperature on a rocker to mimic platelet storage conditions. PEVs isolated from these preparations displayed similar size, morphology, and cellular uptake across groups, but their biological effects diverged. Female-derived PEVs, particularly from resting platelets, provided the strongest protection against thrombin-induced endothelial barrier disruption, stabilized junctional proteins, and reduced oxidative stress. Compared with female-derived PEVs, male-derived PEVs showed weaker barrier protection but more pronounced modulation of certain inflammatory mediators. In addition, PEVs derived from resting platelets consistently showed stronger protective effects than those from stored platelets, regardless of donor sex. These results highlight that donor sex and platelet storage influence PEV function and underscore the need to account for both when developing PEV-based therapies.

Published Open-Access

yes

Recommended Citation

Kaur, Mandeep; Gupta, Malvika; Gopal, Sowmya Shree; et al., "Donor Sex and Platelet Storage Change the Therapeutic Effects of Platelet-Derived Extracellular Vesicles on Endothelium" (2026). Faculty, Staff and Student Publications. 4524.
https://digitalcommons.library.tmc.edu/uthmed_docs/4524