Rafiq Islam, (Kansas City): Since culturing of human hepatocytes is tricky and cells derived from different donors have a very different genetic make-up, scientists at the University of Pittsburg School of Medicine have successfully generated for the 1st time miniature 3D human livers in the laboratory using induced pluripotent stem cells (iPSCs) technology that differentiated into liver cells, which they called iHeps. The iHeps, when seeded together with fibroblasts and macrophages into rat livers that had been denuded of their own cells, grew into functional 3D mini livers with blood vessels and features of normal liver structures.
In the study published in Cell Metabolism, the group created a genetically engineered mini liver in which they deleted SIRT1 gene to mimic non-alcoholic fatty liver disease (NAFLD). It is a complex disorder that can increase the risk of diabetes, cardiovascular and kidney diseases and potentially lead to liver failure.
NAFLD affects 100 million people in the US alone. Environmental, lifestyle, and genetic factors may all contribute to NAFLD, but the underlying mechanisms are not well understood. However, studies on mice models and on liver samples from NAFLD patients, researchers suspect sirtuin-1 (SIRT1) plays a role.
Researchers observed the typical hallmarks of fatty liver disease that is when exposed to fatty acids; these cells accumulated more fats compared to control. Unfortunately resveratrol, a SIRT1 agonist, which worked very well in mice models, was not effective on these model human mini liver cells. Soto-Gutierrez, the lead author, explained that the reason for this may be that resveratrol increases the activity of the SIRT1 protein, not the SIRT1 gene. In any case, this method of growing mini liver cells will provide a way to screen drugs for many liver diseases as well as molecular studies.