Endothelial cell therapy

Congenital vascular malformations (CVM) are a group of inborn disorders associated with vein or artery defects. These often induce disfiguring lesions in the face and are a great cause of pain and social distress to the affected individuals. Currently there is no definitive therapy for CVM.

A better characterisation of the cellular components of the CVM is required to induce transdifferentiation of the endothelial cells (ECs) in the lesion. The scope of the EU-funded CVM THERAPY (Angiogenesis research to improve therapies for vascular malformations) project is to isolate and characterise the Ecs in the vascular malformations to therapeutically target these lesions.

Researchers isolated capillary, venous and lymphatic Ecs from various biobanked sporadic CMV cases. They used a real-time cellular analysis system to analyse the proliferation of EC from malformations as well as their migratory and angiogenic properties. Preliminary data indicate distinct alterations compared to their normal counterparts.

To selectively halt blood supply in various diseases, scientists are in the process of differentiating Ecs to mesenchymal stem cells, a well-known developmental phenomenon. Emphasis is also being given to the identification of the basic signalling pathways and the transcription factors implicated in these transdifferentiation processes.

From previous work, CVM THERAPY researchers had discovered that TGF-beta drove the endothelial to mesenchymal transdifferentiation and are currently exploring the use of this cytokine to drive CVM EC differentiation. Additionally, they are exploring the utilisation of the transcription factors - serum response factor and myocardin, which are essential for smooth muscle cells.

Taken together, the activities of the CVM THERAPY project demonstrate how the characterisation of Ecs could lead to the development of targeted drugs for CVMs.