Caption: Magnified image of a hepatocyte: nuclei in blue; actin fibers in red, yellow, orange, and green.
Credit: Donna Beer Stolz, University of Pittsburgh
The humble hepatocyte handles a lot of the body’s maintenance and clean up work. It detoxifies the blood, metabolizing medications and alcohol. It secretes important proteins that regulate carbohydrates and fats—including both the good and bad kinds of cholesterol. It’s also the most common cell in one of the few human organs that regenerate: the liver. When this organ is damaged, hepatocytes begin dividing to repair the tissue.
Its regenerative ability is just one reason that Donna Beer Stolz, a microscopist and cell biologist at the University of Pittsburgh, in Pennsylvania, has been studying the hepatocyte for more than 20 years. She captured this image while conducting one of her experiments. As she was carefully scanning a dish of cells, one particular hepatocyte caught her eye. It was perfectly round. Struck by its symmetry and beauty, Stolz snapped pictures of the cell at different layers and then used software to reconstruct and color the image.
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 . 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.
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.