Proof of Concept

With guidance from our Scientific Advisory Board as well as industry drug development experts, HemoShear has conducted a series of Proof-of-Concept (PoC) studies to validate the technology. Our studies demonstrate the re-creation of human vascular biology and disease in the HemoShear device. Also, our studies confirm the positive and negative effects of known human drug successes and failures on the blood vessel system.

CELL SURVIVAL. Human vascular cells survive indefinitely when subjected to hemodynamic (blood-flow) forces in the HemoShear device, as compared with traditional cell cultures in which cells die rapidly.

BLOOD VESSEL STRUCTURE. HemoShear’s technology re-creates the structural anatomy of a blood vessel. That is, under healthy hemodynamic conditions, endothelial cells align themselves in the direction of flow, while smooth muscle cells align themselves perpendicular to flow. Under disease-prone flow conditions, endothelial cells become polygonal and smooth muscle cells become disoriented. The response of vascular cells to hemodynamic flow in the HemoShear device mirrors human vascular anatomy.

BLOOD VESSEL BARRIER FUNCTION. An important function of the endothelium is to regulate vessel permeability, which governs penetration of proteins, gases and other substances through the blood vessel wall. In traditional cell culture, when endothelial cells are exposed to thrombin, permeability or vessel “leakiness” is increased. Importantly, the same concentration of thrombin does not alter vascular permeability in humans. When vascular cells are restored to their in vivo state by exposing them to hemodynamic conditions with HemoShear’s technology, permeability is not altered by the same concentration of thrombin, thus mimicking the human response.

ATHEROPRONE CONDITIONS. By imparting hemodynamic patterns derived from areas in the human vasculature susceptible to atherosclerosis and inflammation, HemoShear’s technology re-creates conditions that mimic early events in atherosclerosis and vascular injury.

MONOCYTE ADHESION, INFLAMMATION. HemoShear’s technology demonstrates increased inflammation under disease-prone vs. healthy hemodynamic conditions as indicated by cytokine secretion profiles and enhanced monocyte adhesion.

ATORVASTATIN (LIPITOR™). Extensive experiments conducted with atorvastatin in HemoShear’s technology have unmasked previously unknown mechanisms that explain atorvastatin’s direct, protective effects on the blood vessel wall. HemoShear’s experiments also confirm mechanisms of atorvastatin’s anti-inflammatory, anti-coagulant and enhanced endothelial barrier function effects, which correlate with clinical studies of statins. See Atorvastatin Case Study.

RECOXAFIB (VIOXX™). HemoShear conducted experiments under hemodynamic flow conditions that demonstrate the pro-inflammatory properties of recoxafib in disease-prone vessel regions, which are consistent with the human response in patients with cardiovascular disease. In comparison, the same experiments conducted in traditional static cell culture conditions did not show an enhanced inflammatory response with recoxafib.

PIOGLITAZONE (ACTOS™). Ongoing analyses of experiments conducted with pioglitazone have unmasked anti-inflammatory properties of this compound.

MINOXIDIL. Minoxidil has presented a paradox to drug researchers. The drug, which was originally developed as a blood pressure medication, has been shown to cause drug-induced vascular toxicity in animals, but has not been shown in humans. In fact, HemoShear’s experiments confirm both sets of observations. That is, HemoShear’s technology explains the mechanism causing toxicity in animal cells, while demonstrating no toxic effect in human cells. This set of experiments, among many others, demonstrates the advantages of HemoShear’s technology in being able to differentiate animal vs. human cell responses.

Other proof of concept studies show that animal cells are often far more sensitive than human cells in response to drug compounds, and frequently the response of animal genes is opposite to the human.