Establishment of preclinical models of vascular malformations to study the effect of bleomycin electrosclerotherapy

Vascular malformations (VMs) are vascular anomalies characterized by abnormal, often highly permeable, highly proliferative and tumor-like blood vessels. Clinically, VMs are divided into low-flow and high-flow malformations, and the optimal treatment strategies depend on the specific type and anatomical location of the anomaly. Bleomycin is one of the most widely used drugs in VM sclerotherapy, but its mechanism of action remains unknown. The aim of this study is to investigate whether reversible electroporation combined with bleomycin or bleomycin electrosclerotherapy (BEST) would increase the effect of VM sclerotherapy. Also, the underlying biological mechanisms by which endothelial cells respond to BEST, which parameters of the electrical pulses and which concentrations of bleomycin are the most effective with minimal side effects have not yet been investigated. The main objective of the proposed project is to assess the therapeutic potential of BEST for the treatment of VM and to investigate its mechanism of action. We will establish and validate in vitro and in vivo murine models of VM, which will then be used to determine the optimal BEST therapy parameters, electrical pulses and bleomycin concentration in vitro. In further experiments, we will investigate the effects of BEST on the morphological and phenotypic characteristics of VM in vitro and finally determine the therapeutic potential of BEST treatment of VM in vivo.