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Alchemy: From liposuction fluid to new liver cells

alchemyHow's this for modern-day medical alchemy: A team led by Stanford's Gary Peltz, MD, PhD, has found a fast, cheap, efficient way for regenerating liver tissue from a patient's own fat cells. Let it be immediately said that the "patients" in this endeavor (described in a just-published study in Cell Transplantation) were mice. But the fat cells that Peltz's team used as starter materials and the liver tissue that grew inside the mice (replacing their own organs, which had experienced severe poisoning not unlike that caused by a Tylenol overdose) were completely human.

The liver - the body’s chemistry set - builds complex biomolecules we need and filters and breaks down waste products and toxic substances we need to get rid of. Unlike most organs, a healthy liver can regenerate itself to a significant extent. But this ability is no match for acute liver poisoning or damage from chronic alcoholism or viral hepatitis. Acute liver failure from acetaminophen (Tylenol) alone takes a toll of about 500 lives every year and accounts for upwards of 60,000 emergency-room visits annually.

That begets an ongoing, life-threatening liver shortage. From my release on the study:

Some 6,300 liver transplants are performed annually in the United States, with another 16,000 patients on the waiting list. Every year, more than 1,400 people die before a suitable liver can be found for them. While it can save lives, liver transplantation is complicated, risky and, even when successful, fraught with aftereffects. Typically, the recipient is consigned to a lifetime of taking immunosuppressant drugs to prevent organ rejection.

Making new livers out of a patient's own readily retrieved fat tissue could help plug the gap between the number of available donor livers for transplantation and the number of people in dire need of that procedure. It might also go a long way to alleviating the requirement for lifelong immunosuppressant therapy afterward.

Peltz's team obtained adipose stem cells, which ordinarily grow up to be fat cells, from fat-filled fluid removed during routine liposuction procedures. The team then put these cells through a series of biochemical hoops that caused them to change their minds and decide to be liver cells instead.

That's not easy. ("We had to work hard to convert them to liver cells," Peltz told me.) But it's been done before. The problem was that previous fat-to-liver methods took longer than a patient with acute liver failure can survive, and were inefficient and expensive to boot. Using a new technique, Peltz's group was able to get enough good liver cells for the next regenerative step - injecting the cells into mice's liver cavities - within seven or eight days. A month later the mice exhibited healthy human liver formation and activity. Importantly, inspection at two months out showed no signs of tumor formation, which is a big obstacle to the alternative use of human embryonic stem cells or induced pluripotent stem cells for this purpose.

Peltz hopes to see the new technology enter clinical trials within a couple of years.

Previously: Fortune teller: Mice with 'humanized' livers predict HCV drug candidate's behavior in humans, Free database of drugs associated with liver injury available from NIH and Hepatitis C virus's Achilles heel
Photo by Abode of Chaos

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