The NIH has awarded MIMETAS and the University of Pittsburgh a prestigious SBIR grant to develop a Liver-on-a-Chip platform for high throughput discovery and development. Accurate prediction of hepatotoxicity is a major problem in the development of new drugs leading to high development costs. Animal hepatotoxicity testing is expensive, unsuited to high throughput and overall has unreliable concordance with human hepatotoxicity. MIMETAS scientists have teamed up with the University of Pittsburgh Drug Discovery Institute led by D. Lansing Taylor, Ph.D. to develop a liver-on-a-chip platform of unprecedented throughput, predictivity and usability. “We’re extremely happy to be working with Lans and his team on this project”, says Dr. Anthony Saleh of MIMETAS. “Prof. Taylor is a frontrunner in developing in vitro liver cultures and has vast experience with microfluidic techniques." “We were extremely impressed when we learned about the MIMETAS OrganoPlate platform”, commented Prof. Taylor. “It enables High Throughput, 3D co-culture with a vascular and hepatic compartments, as well as ease of handling. There is really no equivalent in the Organ-on-a-Chip space”.
About the project
In the project the team will adapt the sequentially layered, self-assembly liver model (SQL-SAL), developed by the University of Pittsburgh Drug Discovery Institute, into MIMETAS’ high throughput microfluidic OrganoPlate®. The resulting platform will contain 96 x 3D microfluidic co-cultures of human primary or iPSC hepatocytes with three non-parenchymal human liver cell types. In OrganoPlates®, extracellular matrix (ECM) gels can be freely patterned in microchambers through the use of the PhaseGuide™ technology. PhaseGuides™ (capillary pressure barriers) define channels within microchambers that can be used for extracellular matrix deposition or medium perfusion. The microfluidic channel dimensions not only allow solid tissue and barrier formation, but also perfused tubular endothelial vessel structures (vascularization). Utilizing the PhaseGuide™ technology we are able to engineer our culture to mimic the structure of the liver sinusoid by culturing hepatocyte and stellate cells in an extracellular matrix protein gel, fed by microfluidic nutrient perfusion from an adjacent endothelial and Kupffer cell-lined blood vessel mimic. The platform will report multi-parameter high-content imaging based readouts of toxicity including mitochondrial function and steatosis, creating an unparalleled platform for assessment of pharmaceutical and environmental hepatotoxicity.
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