Therapeutic Angiogenesis – B2B project

Therapeutic Angiogenesis

The B2B partner Andrea Banfi directs the Cell and Gene Therapy group at Basel University Hospital, in the Departments of Biomedicine and of Surgery. His research focus is the understanding of the basic principles governing the growth of blood vessels and translating this knowledge into the development of novel therapies. We asked him to introduce us to the concept of therapeutic angiogenesis.  

New blood vessels forming from pre-existing vessels.
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“Therapeutic angiogenesis is the generation of blood vessels for therapeutic applications. Today, besides the application in tissue-engineering in vitro, like the one in B2B, there is also an increasing interest in the vascularization of ischemic tissues, in which the blood supply is reduced and needs to be restored for the normal organ function.

There are no pharmacological cures for this disease today. Only surgical interventions can substitute blocked arteries (e.g. by-pass surgery), but results are unsatisfactory, both because not every patient can be operated, and because the opened vessels re-close with time. By understanding how angiogenesis is regulated in nature, we might exploit similar signals to trigger new vascular growth directly in the tissue to generate a sort of long-lasting “biological by-pass”.

Common signals are molecules like the growth factor VEGF, but the body tightly regulates their production and avoids exceeding potentially harmful thresholds. To induce therapeutic blood vessels formation, it is necessary to exceed, under limited circumstances, the dose-limit that the body imposes. In our lab, we are investigating the optimal mix of stimuli, doses and duration of treatment to trigger efficient and long-lasting blood vessels formation.

During the very first tests, back in the early 2000s, therapies with VEGF failed to show efficacy in patients at safe doses. Subsequent retrospective analyses identified several issues underlying the discrepancy between the obvious biological function of VEGF and its difficulty as a drug. An important aspect relates to the fact that VEGF binds tightly to extracellular matrix and remains localized in the micro-environment around each producing cell. Therefore, it is important to ensure a homogeneous distribution of production levels in the tissue, otherwise a few hot spots – in which the local dose is toxic – will compromise safety, while the areas that don’t reach an effective dose compromise efficacy.

In our lab, we are currently working to overcome this issue. Homogeneous distributions of VEGF are rather hard to get, so we are exploring ways to stop the onset of the toxic behavior only in the hot spots. By administrating specific drugs during the critical first weeks after the therapy, we can block the aberrant angiogenesis while keeping the desired one. It’s a long way before reaching the clinical application, but I’m confident that we will finally find a way to apply angiogenesis in the fight against ischemia. “

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