Left Menu
Development News Edition

GM human mini livers to help test medicines

PTI | Washington DC | Updated: 07-08-2019 17:05 IST | Created: 07-08-2019 17:05 IST
GM human mini livers to help test medicines

In a first, researchers have grown genetically modified miniature livers in the laboratory, to emulate human liver disease progression and test medicines. The researchers at the University of Pittsburgh in the US transformed genetically engineered human cells into functional, three-dimensional (3D) liver tissue that mimics non-alcoholic fatty liver disease (NAFLD) -- a condition involving fat buildup in the liver, which can lead to cirrhosis or even liver failure.

"This is the first time we can create genetically engineered human mini livers with a disease using stem cells in the lab," said Alejandro Soto-Gutierrez, an associate professor at the University of Pittsburgh. That's important not only for understanding what causes the disease and how it progresses, but also for testing therapeutics, according to the study published in the journal Cell Metabolism.

It's common for drugs to fail in clinical trials, despite promising results in mice. For instance, the drug Resveratrol, which acts on SIRT1 proteins commonly associated with NAFLD, was effective in mouse models, but failed in human clinical trials.

"Mice aren't humans. 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 customised human liver is advantageous," Soto-Gutierrez said. First, the researchers genetically engineered normal human skin cells to express a chemically activated switch that could tamp down the SIRT1 gene.

They reprogrammed the cells back to their stem cell state and turned them into liver cells. After that, they seeded the genetically engineered human liver cells into rat livers stripped of their own cells, where they blossomed into functional 3D mini livers, with blood vessels and other structural features of a normal organ.

That structure is part of what distinguishes mini livers from 'organoid' cultures -- tiny balls of cells that self-assemble to replicate simplified organ function -- although the mini livers lacked the distinct zones of metabolic function that normal livers have. Once the mini livers were mature, the researchers flipped the genetic switch to suppress the SIRT1 gene, and the bioengineered mini livers started to mimic the metabolic dysfunction observed in tissues from patients with fatty liver disease.

However, just like the clinical trials, Resveratrol wasn't effective in the lab-grown livers either. The key, Soto-Gutierrez explained, is that Resveratrol boosts the activity of SIRT1 proteins, not SIRT1 genes.

If SIRT1 gene expression is suppressed -- like it is in his bioengineered livers, and perhaps also NAFLD patients -- there isn't any protein to act on, so the drug won't work. It's targeting the wrong step. "That's an insight that could only come from studying functional human tissue," Soto-Gutierrez said.

Genetically engineered, lab-grown mini livers provide a ready and reliable test-bed for drugs at all stages of disease progression, resaerchers 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.


TRENDING

OPINION / BLOG / INTERVIEW

Post-COVID-19 Nigeria needs a robust Health Management Information System to handle high disease burden

Nigeria is among a few countries that conceptualised a health management information system HMIS in the early 90s but implementation has been a challenge till date. Besides COVID-19, the country has a huge burden of communicable and non-com...

Morocco COVID-19 response: A fragile health system and the deteriorating situation

Learning from its European neighbors, Morocco imposed drastic measures from the initial stages of the COVID-19 outbreak to try to contain its spread. The strategy worked for a few months but the cases have surged after mid-June. In this sit...

COVID-19: Argentina’s health system inefficiencies exaggerate flaws of health information system

You can recover from a drop in the GDP, but you cant recover from death, was the straightforward mindset of Argentinas President Alberto Fernndez and defined the countrys response to COVID-19. The South American nation imposed a strict...

Rwanda’s COVID-19 response commendable but health information system needs improvement

Rwanda is consistently working to improve its health information system from many years. However, it is primarily dependent on the collection and reporting of health data on a monthly basis. Besides, evaluation studies on Rwandas HIS publis...

Videos

Latest News

Costa Rica's Alvarado pitches IMF package as economic lifeline

Costa Rican President Carlos Alvarado predicted more economic pain without a major aid package from the International Monetary Fund IMF, arguing that inflation and unemployment would get worse without it, he told Reuters in an interview on ...

Biden courts crucial Black voting bloc in key state of North Carolina

Democratic presidential nominee Joe Biden on Wednesday said Black turnout was the linchpin to his hopes of winning the White House in November and reversing economic and social inequities that have held back African-Americans. Noting that t...

Saudis warn U.N. of oil spot in shipping lane near decaying Yemen tanker

Saudi Arabia warned the U.N. Security Council on Wednesday that an oil spot had been seen in a shipping transit area 31 miles 50 km west of a decaying tanker that is threatening to spill 1.1 million barrels of crude oil off the coast of Yem...

PREVIEW-Rugby-England v France, old v new in European semis

Rugbys Champions Cup semi-finals on Saturday feature not only two classic Anglo-French clashes but also matches pitting heavyweight teams looking to enlarge their European trophy collection against sides desperate to join the top table.Sara...

Give Feedback