July 31, 2018

Liver-derived Endothelial Cells

A glass-based, continuously zonated and vascularized human liver acinus microphysiological system (vLAMPS) designed for experimental modeling of diseases and ADME/TOX

Li X, George SM, Vernetti L, Gough AH, Taylor DL | University of Pittsburgh
Lab Chip. doi: 10.1039/c8lc00418h

The vLAMPS is a human, biomimetic liver MPS, in which the ECM and cell seeding of the intermediate layer prior to assembly, simplifies construction of the model and makes the platform user-friendly. This primarily glass microfluidic device is optimal for real-time imaging, while minimizing the binding of hydrophobic drugs/biologics to the materials that constitute the device. The assembly of the three layered device with primary human hepatocytes and liver sinusoidal endothelial cells (LSECs), and human cell lines for stellate and Kupffer cells, creates a vascular channel separated from the hepatic channel (chamber) by a porous membrane that allows communication between channels, recapitulating the 3D structure of the liver acinus. The vascular channel can be used to deliver drugs, immune cells, as well as various circulating cells and other factors to a stand-alone liver MPS and/or to couple the liver MPS to other organ MPS. We have successfully created continuous oxygen zonation by controlling the flow rates of media in the distinct vascular and hepatic channels and validated the computational modeling of zonation with oxygen sensitive and insensitive beads. This allows the direct investigation of the role of zonation in physiology, toxicology and disease progression. The vascular channel is lined with human LSECs, recapitulating partial immunologic functions within the liver sinusoid, including the activation of LSECs, promoting the binding of polymorphonuclear leukocytes (PMNs) followed by transmigration into the hepatic chamber. The vLAMPS is a valuable platform to investigate the functions of the healthy and diseased human liver using all primary human cell types and/or iPSC-derived cells.

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July 25, 2018

45 minutes

Isolation, Characterization, and use of DonorMatched™ Primary Human Liver Cells in the study of NAFLD/NASH

Sharon C. Presnell, PhD | President, Samsara | CSO, Organovo

Today’s research strategies in the study of human liver biology and disease require access to cell samples that capture the complexity of the tissue of origin as well as the heterogeneity of the human donor population. Matched sets of primary human cells are now available from a spectrum of donors, including patients with confirmed NAFLD/NASH. How are these reagents being utilized today? How might their availability power your research?