Tissue Model Reveals Key Players in Liver Regeneration By tracing the steps of liver regrowth, MIT engineers are striving to harness the liver’s regenerative abilities to help treat chronic disease. The human liver has incredible regeneration capabilities: Even if up to 70% of it is removed, the
By tracing the steps of liver regrowth, MIT engineers hope to harness the liver’s regenerative abilities to help treat chronic disease. Hepatocytes, the one pictured here, are the main functional cells of the liver. Credit: NIHengineers are striving to harness the liver’s regenerative abilities to help treat chronic disease.
Using the new model can yield information that couldn’t be gleaned from studies of mice or other animals, whose biology is not identical to that of humans, says Sangeeta Bhatia, the leader of the research team. From studies in mice, researchers have learned a great deal about some of the regeneration pathways that are activated after liver injury or illness. One key factor is the reciprocal relationship between hepatocytes and endothelial cells, which line the blood vessels. Hepatocytes produce factors that help blood vessels develop, and endothelial cells generate growth factors that help hepatocytes proliferate.
The chip is designed so that molecules such as growth factors can flow between the blood vessels and the liver spheroids. This setup also allows the researchers to easily knock out genes of interest in a specific cell type and then see how it affects the overall system. The MIT team found high levels of this molecule, which is also involved in zebrafish regeneration, in their liver regeneration system. By knocking out the gene for PGE2 biosynthesis in endothelial cells, the researchers were able to show that those cells are the source of PGE2, and they also demonstrated that this molecule stimulates human liver cells to enter the cell cycle.
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