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Leprosy spurs growth in armadillo livers, offering clues to organ regeneration

Armadillos stash a secret under their shells—their liver grows dramatically when they are infected with the bacterium that causes leprosy in people. This oddity, revealed in a new study, may provide clues about how the body controls liver regeneration and how to jump-start the process in people.

The finding is “very cool,” says hepatologist Alejandro Soto-Gutiérrez of the University of Pittsburgh School of Medicine, who wasn’t connected to the research. Almost all animal work on liver regeneration involves mice or rats, he notes, so “it’s refreshing” that scientists are learning from a different species that may furnish novel insights.

The liver is the body’s regeneration champ, able to rebuild after injuries and illness. If a person donates a kidney, a replacement does not sprout in its place. But even if two-thirds of a donor’s liver is removed for transplantation, the remainder will regrow into a full-size organ. However, scientists don’t understand how to trigger this renewal in patients whose livers are failing because of cirrhosis or other conditions.

Enter leprosy. Almost a decade ago, regeneration biologist Anura Rambukkana of the University of Edinburgh and colleagues found leprosy-causing bacteria invade cells called Schwann cells that embrace neurons. Once the bacteria have settled into their new home, they spur the cells to revert to a less mature developmental state, becoming more like stem cells.

But those experiments were on mouse cells in a dish. Would the same process occur in an actual animal?

That question “kept me awake at night,” Rambukkana says, because leprosy bacteria do not grow well in mice or other standard lab animals. Then he recalled that the microbes for the study came from a facility in Louisiana, where researchers were rearing them in nine-banded armadillos, which are a prime host for the bacteria.

Because the microbes dwell in the animals’ livers, Rambukkana contacted one of the scientists at the facility to ask whether he had noticed anything unusual about the organs in infected armadillos. “He said, ‘We always see that the liver is bigger,’” Rambukkana says. “I went crazy.”

The new study confirms that observation. The livers of armadillos infected with leprosy bacteria are about one-third larger than those of their uninfected counterparts, Rambukkana and colleagues report today in Cell Reports Medicine. Moreover, the liver does not just expand higgledy-piggledy in the animals. The enlarged organs retain their distinctive anatomy, with the correct number of lobes and the characteristic honeycomblike arrangement of subunits. Dissecting how the animals’ livers keep growing might help researchers better understand the mechanisms of regeneration in the human liver.

Patients with infections or other liver conditions can develop tumors and accumulate scar tissue that can hamper the organ’s activity. However, the researchers detected no signs of either problem in the armadillos. What’s more, their analysis of several liver proteins suggested the organs were working properly.

To probe how the liver bulks up, Rambukkana and colleagues measured gene activity in infected and uninfected animals. Like the Schwann cells in their previous work, liver cells in armadillos that harbored the bacteria became more like stem cells. The gene activity in an infected animal’s liver resembled the pattern in the still-forming liver of a human fetus.

“These tiny bacteria know how to grow a functional liver,” Rambukkana says. For the microbes, a bigger liver is probably advantageous because it provides more living space, he says. Scientists might be able to harness the mechanism to induce regeneration in people with liver disease.

Still, the research “leaves a lot of questions” says George Michalopoulos, a liver regeneration investigator also at the Pitt School of Medicine. For instance, he says, the scientists need to show that the liver isn’t larger in the infected armadillos just because “it becomes loaded with bacteria.”

And before this anatomical anomaly can be exploited to develop potential therapies, researchers will need to resolve another issue. “The bacteria have figured out how to fool the [liver cells] into giving them shelter,” says liver biologist Udayan Apte of the University of Kansas Medical Center. “How do the bacteria manage not to kill the cells but instead make them divide?”

Despite, these challenges, Apte says he’s excited by the approach’s promise. The research shows “the liver can remain functional and divide and regenerate at the same time.”

Source: Science Mag