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Updated: Sep 10, 2025

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
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Factor VIIa-released extracellular vesicles attenuate joint bleed-induced hemophilic arthropathy

Padmavathi Kavadipula1, Shiva Keshava1, Kaushik Das1,2

  • 1Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX.

Blood
|August 20, 2025
PubMed

Repeated bleeding into joints in hemophilia leads to chronic inflammation that plays a central role in the pathogenesis of hemophilic arthropathy (HA). Our recent studies revealed that factor VIIa (FVIIa) treatment releases extracellular vesicles from endothelial cells (eEVs) and FVIIa-released eEVs exhibit anti-inflammatory and barrier-protective functions. The present study was undertaken to investigate the effect of FVIIa-released eEVs on HA and the mechanism of their protective effect. Joint bleeding in hemophilia (F8-/-) mice was induced by a needle puncture injury. Injured mice were treated with saline, control eEVs, or FVIIa-released eEVs, and the changes in the knee joints were analyzed by gross examination of knees as well as histological and immunohistochemical analysis. Joint tissues were examined for evidence of synovial hyperplasia, macrophage infiltration, neoangiogenesis, cartilage degeneration, and chondrocyte apoptosis. The data showed that treatment of mice with control eEVs had no significant effect on the development of HA, whereas treatment with FVIIa-released eEVs markedly reduced all pathological features of joint bleed-induced HA. Incorporation of microRNA10a (miR10a) inhibitor into FVIIa-released eEVs abrogated the protective effect of FVIIa-released eEVs on HA. More importantly, loading miR10a mimic into control eEVs conferred a protective effect. Administration of miR10a-containing FVIIa-released eEVs or control eEVs loaded with miR10a mimic was found to abrogate joint bleed-induced interleukin-6 production in the synovium. miR10a in eEVs had no effect on hemostasis. Cumulatively, our data indicate that EVs containing miR10a that effectively suppress synovial inflammation would have immense therapeutic value in treating HA.

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