Harnessing Stem Cells for Blood Vessel Regeneration

Vascugen recently announced that it had licensed stem cell technology for blood vessel regeneration at IU School of Medicine, which could lead to new treatment options for patients suffering from Peripheral Artery Disease and Critical Limb Ischemia. We caught up with Carter Cliff, CEO, Vascugen to learn more about the technology and the science behind it. 

Anna MacDonald (AM): Can you tell us about Peripheral Artery Disease and why it is such an important condition to develop new treatments for?

CC: Peripheral artery disease (PAD) is a progressive hardening of the arteries that can lead to reduced or blocked blood flow. Hundreds of millions of patients worldwide are affected by the condition, with an estimated three million new cases diagnosed per year in the US. The standard of care involves lifestyle improvement and medications to lower cholesterol and blood pressure, control blood sugar, prevent clots, and manage pain. Many patients undergo angioplasty or bypass surgery.

A significant subset of PAD patients are nonresponsive to these treatments. They can progress to a severe form of the disease known as critical limb ischemia (CLI), which is characterized by severe blockage of the arteries in the lower extremities. Patients suffering from CLI have few options and often require major surgery to amputate the affected region of the limb. Of those who receive an amputation, more than half die within five years.

Approved medications and medical-device base treatments have not been able to address the end-stage CLI condition. Experimental treatments have been primarily focused on use of cells or growth factors hypothesized to stimulate endogenous vascular regeneration. These approaches have either not worked or shown limited potential, arguably due to CLI patients’ reduced or lost intrinsic capacity to form new blood vessels, leaving few cells for these treatments to act upon.

Vascugen is taking a new approach. We are developing a cell therapy product that, when delivered to the ischemic tissue, directly forms new micro-vessels. Based on this mechanism, these unique cells are potentially able to restore blood flow to the tissue.

AM: What role do endothelial cells play in the formation of new blood vessels?

CC: Vascugen’s scientific founder and chief scientific officer, Dr. Mervin Yoder, was the first to discover that the endothelial lining of blood vessels contains a rare vascular progenitor cell that is both necessary and sufficient for formation of new blood vessels. It is important to note that there are many types of endothelial cells found throughout the body. What is unique about the stem cell discovered by Dr. Yoder is the clonal and proliferative properties that allow it to give rise to new healthy vasculature. These are the properties we have incorporated into the development of our therapeutic product, based upon proprietary intellectual property (IP) exclusively licensed, in part, from the University of Indiana to Vascugen.

AM: How can this process be harnessed to treat patients?

CC: In a healthy individual, the body normally grows new blood vessels to supply oxygen-starved tissues. However, CLI patients are deficient in this capacity, due to a degenerative condition involving the reduction or loss of the vascular progenitor cell type necessary for survival and function of the surrounding tissues. This condition is potentially amenable to intervention by replacement of the target vascular progenitor cell that has been lost.

Several other groups are taking the same approach in different indication areas for unmet needs that are nonresponsive to traditional medications or medical device-based interventions. Two examples include replacement of dopamine-secreting neurons in patients with Parkinson’s disease and replacement of photoreceptors in patients with Retinitis Pigmentosa.

With an understanding of the characteristics of our target vascular progenitor cell, and methods to manufacture this cell into our product, we can harness its natural potency for repair of the vasculature. Our objective is to restore blood flow to oxygen-starved tissues and thus alleviate the condition.

AM: What future work do you have planned?

CC: Vascugen is currently focused on manufacture scale-up and pre-clinical evaluation of our product candidates for CLI as a first-target indication. Looking forward, we are establishing partnerships with leading regenerative medicine, pharmaceutical, and medical device companies to advance a pipeline of applications where our product can have an impact. These include other target indications where vascular repair is needed as well as opportunities to apply our technology and know-how to enhance efforts in tissue engineering, bio-printing, gene-editing, and other areas.

Carter Cliff was speaking to Anna MacDonald, Science Writer for Technology Networks.