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Updated: Apr 21, 2026
A Model for Encephalomyosynangiosis Treatment after Middle Cerebral Artery Occlusion-Induced Stroke in Mice
Published on: June 22, 2022
Myoblast-mediated gene therapy improves functional collateralization in chronic cerebral hypoperfusion
Nils Hecht1, Aiki Marushima1, Melina Nieminen1
1From the Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Germany (N.H., A.M., M.N., I.K., J.W., P.V.); and Baxter Laboratory for Stem Cell Biology, Stanford University, CA (G.v.D.).
Myoblast delivery of vascular endothelial growth factor-A (VEGF) enhanced indirect revascularization for chronic cerebral hypoperfusion. This gene therapy improved blood flow and reduced stroke-related brain damage in a mouse model.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Vascular Biology
Background:
- Direct extracranial-intracranial bypass surgery for cerebral hemodynamic compromise is limited by complications.
- Indirect revascularization procedures like encephalomyosynangiosis (EMS) are safer but less effective hemodynamically.
- Myoblast-mediated gene transfer offers a novel approach to induce therapeutic collateralization.
Purpose of the Study:
- To evaluate myoblast-mediated delivery of vascular endothelial growth factor-A (VEGF) to enhance EMS in a chronic cerebral hypoperfusion model.
- To assess the impact of VEGF-expressing myoblasts on cerebral hemodynamics, collateralization, and stroke protection.
Main Methods:
- Adult mice underwent permanent unilateral internal carotid artery occlusion.
- Surgical grafting of EMS with implantation of myoblasts expressing VEGF164 or an empty vector (EV) was performed.
- Cerebral blood flow, collateralization, angiogenesis, and cortical infarction were assessed using advanced imaging techniques.
Main Results:
- VEGF-expressing myoblasts significantly improved hemodynamic rescue and EMS take rate compared to controls.
- Enhanced angiogenesis of mature cortical microvessels was observed below the EMS.
- A 25% reduction in cortical infarction size was achieved after experimental stroke.
Conclusions:
- Myoblast-mediated VEGF supplementation at the EMS site can improve surgical revascularization outcomes.
- This approach offers potential protection against ischemic stroke by promoting therapeutic collateralization.
