Document Type
Article
Publication Date
3-26-2026
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.
Recommended Citation
Kaur, Mandeep; Gupta, Malvika; Shree Gopal, Sowmya; Wade, Charles E.; Cardenas, Jessica C.; and Srivastava, Amit K., "Donor Sex and Platelet Storage Change the Therapeutic Effects of Platelet-Derived Extracellular Vesicles on Endothelium" (2026). Cardeza Foundation for Hematologic Research. Paper 99.
https://jdc.jefferson.edu/cardeza_foundation/99
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Language
English
Comments
This article is the author’s final published version in Blood Vessels, Thrombosis and Hemostasis, Volume 3, Issue 2, 2026, Article number 100148.
The published version is available at https://doi.org/10.1016/j.bvth.2026.100148. Copyright © 2026 American Society of Hematology.