Leech Extract Enhances the Pro-Angiogenic Effects of Endothelial Cell-Derived Exosomes in a Mouse Model of Ischemic Stroke
Basic science / preclinical published in Curr Issues Mol Biol (2025)
Abstract
BACKGROUND: Intercellular communication, facilitated by exosomes (Exos) derived from endothelial cells (ECs), significantly influences the regulation of angiogenesis. Leech extract significantly reduces ischemia-reperfusion injury, promotes angiogenesis, and improves neurological function in mice with stroke. However, further investigation is required to determine whether leech promotes angiogenesis through EC-Exo. OBJECTIVE: This study aims to further explore whether leech regulates Exos to promote the establishment of collateral circulation in mice with ischemic stroke (IS) and the specific mechanisms involved. METHODS: Here, we utilized an in vitro co-culture system comprising ECs and pericytes to investigate the impact of Leech-EC-Exo on enhancing the proliferation and migration of mouse brain microvascular pericytes (MBVPs). We further established an in vivo mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) to investigate the effects and underlying mechanisms of leech on collateral circulation establishment. RESULTS: The findings demonstrated that leech significantly enhanced the in vitro cell migration number and migration number of pericytes. Therefore, it can also enhance the effect of EC-Exo on improving the infarct area and gait of mice, as well as modulating the HIFα-VEGF-DLL4-Notch1 signaling pathway to promote cerebral angiogenesis and facilitating the stable maturation of neovascularization in vivo. CONCLUSIONS: These results suggest that leech has the potential to enhance collateral circulation establishment, and its mechanism may involve the modulation of miRNA content in Exos and the promotion of signaling pathways associated with angiogenesis and vascular maturation.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Demonstrates leech extract enhances angiogenic effects of endothelial-cell-derived exosomes via HIFalpha-VEGF-DLL4-Notch1 signaling in a middle-cerebral-artery-occlusion mouse model. Improves infarct area, gait, and collateral-circulation maturation.
Por qué esto importa para la hirudoterapia
Este estudio investigó si el extracto de sanguijuela promueve la angiogénesis mediante la modulación de exosomas derivados de células endoteliales (EC-Exos), utilizando tanto un sistema de cocultivo in vitro de células endoteliales y pericitos como un modelo in vivo de oclusión de la arteria cerebral media/reperfusión (MCAO/R) en ratón de accidente cerebrovascular isquémico. Los EC-Exos enriquecidos con sanguijuela aumentaron la proliferación y migración de pericitos in vitro, redujeron el área de infarto, mejoraron la marcha y promovieron la angiogénesis cerebral in vivo, implicando los autores a la vía de señalización HIFα-VEGF-DLL4-Notch1 y a la modulación del contenido de miARN exosómico. Para el dominio de ASH, esto aporta evidencia preclínica de que los componentes derivados de la sanguijuela podrían favorecer la neovascularización y la circulación colateral, ampliando la relevancia del secretoma de la sanguijuela más allá de la anticoagulación. La advertencia honesta es que se trata de un estudio preclínico en ratón y en cultivo celular que emplea un extracto de sanguijuela de composición no especificada; no se identifica ninguna molécula específica derivada de la sanguijuela, no se aplican sanguijuelas vivas con fines terapéuticos, y la relevancia clínica permanece sin comprobar.
Citación
Leech Extract Enhances the Pro-Angiogenic Effects of Endothelial Cell-Derived Exosomes in a Mouse Model of Ischemic Stroke.
Cao Y et al. · Current issues in molecular biology, 2025
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026