iMPCs: Cell Reprogrammers Take Aim at Liver Disease

Cross-section of mouse liver

Caption: Cross-section of mouse liver containing iMPC-derived human liver cells (red), some of which are proliferating (green). All cell nuclei appear blue.
Credit: Milad Rezvani, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco

Over the past few years, researchers have learned how to reprogram skin or blood cells into induced pluripotent stem cells (iPSCs), which have the ability to differentiate into heart, nerve, muscle, and many other kinds of cells. But it’s proven a lot more tricky to coax iPSCs (as well as human embryonic stem cells) to differentiate into mature, fully functional liver cells.

Now, NIH-funded researchers at the University of California, San Francisco (UCSF) and the Gladstone Institutes appear to have overcome this problem. They have developed a protocol that transforms human skin cells into mature liver cells that not only function normally in a lab dish, but proliferate after they’ve been transplanted into mice that model human liver failure [1]. This ability to proliferate is a hallmark of normal liver cells—and the secret to the liver’s astounding capacity to regenerate after infection or injury.

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Put This Liver To The Test

A photo of a petri dish holding a piece of tissue.

Artificial Liver
Source: NIBIB, NIH

Growth of blood vessels (red) enables implanted human ectopic artificial livers (HEALs) to grow and function in the mouse. This miniature human liver was removed from a HEAL-humanized mouse. Mice implanted with these organs are particularly useful for monitoring drug metabolism, drug-drug interactions, and predicting how certain drugs can damage and destroy the human liver.