In a recent study, researchers from the University of Pittsburgh School of Medicine successfully grew human liver in a controlled environment inside a laboratory. These miniature livers were genetically modified to exhibit the traits that the researchers wanted to study. The primary aim of the study was to simulate liver disease progression to better understand and hence find a cure for it.
A summary of the findings from the study was published in the science magazine Cell Metabolism. Researchers from the Pittsburgh School of Medicine genetically modified the cells from a human liver and made the miniature liver models to exhibit the NAFLD – Non-alcoholic fatty liver disease.
NAFLD is a rising problem as more and more people have reportedly contracted it. Fat builds up uncontrollably in the liver and this can eventually lead to liver failure. The rising obesity rates in the US are also causing fat deposit issues.
“This is the first time we can create genetically engineered human mini livers with a disease using stem cells in the lab,” said senior author Alejandro Soto-Gutierrez.
Mr. Gutierrez serves as an associate professor of pathology at Pittsburgh School of Medicine and is a member of the McGowan Institute for Regenerative Medicine and the Pittsburgh Liver Research Center.
Despite good results in mice, it is not new that a drug fails during its clinical trials hence the miniature liver that has been formed holds a lot of promise. Not only will it help in understanding the liver and the disease progression it will also help in the therapeutics testing.
“Mice aren’t humans,” Soto-Gutierrez said. “We are born with certain mutations, polymorphisms, that will predispose us to certain diseases, but you can’t study polymorphisms in mice, so making a mini customized human liver is advantageous.”
The team headed into the study by engineering human skin cells at first, the cells expressed a chemically controlled initiation that could suppress the SIRT1 genes expression. The cells were subsequently put into a stem cell state and turned into liver cells. The liver cells were inserted into liver cells of mice.
The structural shape is a breakthrough finding of modern science as it is the shape which distinguishes it from other organ cultures which just perform similarly but don’t exactly look the same. Here too the mini livers were not the same as they did not have the metabolic function zones that actual human livers have.
When the mini livers had matured into a functioning organ the researchers used the chemical switch embedded in the cells to suppress the SIRT1 gene. As a result, the mini livers showed the same problem as the livers of patients with fatty liver disease do.
The study shed light on the matter as just like the clinical trials, Resveratrol wasn’t effective in the lab-grown livers either.
Soto-Gutierrez explained that the Resveratrol had a wrong approach to the problem as it boosted the activity levels of the SIRT1 proteins instead of targeting the SIRT1 genes. If the gene is suppressed in the first place there won’t be any protein available on which the drug can act and preferred results can be achieved.
“That’s an insight that could only come from studying functional human tissue,” Soto-Gutierrez said.
“These mini livers aren’t ready for clinical applications like transplantation anytime soon, but I imagine in the future we can make human livers where you can order what kind of function you want, or even enhance function,” Soto-Gutierrez added.
This research proves that human-made livers that could solve any issue related to livers or at least will be able to make them understand how the medication will work and will ultimately help in finding a permanent solution for liver-related issues.