3D bioprinting of liver tissue models

National Center For Advancing Translational Sciences

Investigators

Abstract

The groups at UPitt and NCATS have been working on re-engineering the current 3D, chip-based, 4 liver cell vLAMPS NAFLD disease model developed at UPitt to a bioprintable 12-well transwell Liver Acinus model (BpLAMPS) for use as a medium and high throughput drug screening platform. So far, the UPitt group has optimized and verified stellate cell activation as a NAFLD disease progression marker when cultured 8-10 days in the presence of exogenously added molecular drivers of liver disease. In response to the addition of disease drivers including fatty acids, increased glucose, TGF-, and LPS, stellate cells become fibrogenic, indicated by increased smooth muscle actin (SMA) expression. High Content Screening (HCS) and immunofluorescence will monitor SMA expression. Alternate fibrosis markers (stellate cell proliferation, pro-collagen secretion) were also evaluated and shown expected responses. Work is ongoing at UPitt to assess the pharmacological effect of control drugs to reduce fibrogenic transformation consistent with a reversal or slowing of disease progression, including Sorafenib, Cenicriviroc, Simtuzumab and Selonsertib which have been developed and tested in the clinic as antifibrotic agents in the BpLAMPS model.