For more than a decade, Cincinnati Children’s Hospital Medical Center has been making miniature human organs, called organoids, in a lab. New research published in the journalCell shows just how important these tiny, but functional mini organs are.
The study is one of the earliest applications for looking at human disease, and involves a miniature liver. It helps explain why some obese people who have Type 2 diabetes and a condition which builds up excess fat around their liver (called NAFLD) can develop life-threatening liver inflammation, scarring and sometimes liver cancer.
“The team’s experiments ultimately revealed that a single gene variant — GCKR-rs1260326 TT — acts as a dangerous double agent," a Cincinnati Children’s blog explains. "When the liver is functioning in diabetic conditions (high glucose and high insulin levels), the presence of this variant sharply accelerates NAFLD fat accumulation. But when a liver is working within a healthy blood-sugar balance, that same variant actually helps prevent liver scarring more effectively than NASH livers that carry the normal gene.
Dr. Takanori Takebe, MD, with research appointments in Cincinnati and Japan, is one of the pioneers in the organoid field. He and his team create mini organs from human stem cells and customize them to reflect specific disease conditions. WVXU interviewed him in 2018.
In this study, the research team grew liver organoids from the cells of 24 donors.
How can this study improve treatment?
The Children’s blog says, “The recent research found a widely prescribed diabetes treatment — metformin — made liver organoid function even worse when the gene variant was present. But replacing metformin with a combination of two drugs, nicotinamide riboside (NR) and nitazoxanide (NTZ) appears to stabilize the organoids’ function.”
