Development of a Hemodynamic Co-Culture Liver System for Drug Discovery and Assessment

This grant was awarded by the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH in May 2011. This Phase I SBIR grant funds the development of a rodent liver surrogate system using HemoShear's proprietary technology platform to mimic in vivo physiology by applying liver-specific blood flow shear stress forces (hemodynamics) and other physiologically relevant factors to a combination of liver cell types. The aim of this research is to develop a rodent system that will provide pharmaceutical companies with a more predictive and relevant alternative to current monoculture approaches and to provide researchers with a more physiologically accurate way to assess drug metabolism, drug-drug interaction, mechanism-of-action of drug efficacy and pre-clinical safety/toxicity in the rodent liver. This work will provide the foundation for development of a more advanced human liver surrogate system using the HemoShear technology.

Specific Aims

Aim 1: To combine rat liver sinusoidal endothelial cells (SEC) with hepatocytes (HC) in a co-culture system exposed to liver hemodynamic flow conditions.

Aim 2: To demonstrate that the liver co-culture system under hemodynamic flow mimics in vivo biological response more closely than HC/SEC co-cultures under conventional static conditions.

Aim 3: To demonstrate that the liver co-culture system under hemodynamic flow mimics in vivo biological response to hepatotoxic agents more closely than HC/SEC co-cultures under conventional static conditions.

Status Update: In development. Completion expected by first quarter 2012. Current results indicate that the system is performing far superior to current static culture systems. For example, cell morphology and classic differentiation markers are retained, urea and albumin production is maintained over time, Cyp450 activity and inducibility are restored, phase I and phase II metabolism remains intact, transporter protein expression is retained, and primary cell longevity is established.