Scientists have brought the prospect of lab-grown replacement livers a step closer by successfully generating functional human and mouse tissue-engineered liver (TELi).
Both the human and mouse livers were successfully grown in mice, raising hopes that in the future replacement organs could be grown from human patients’ own cells.
The TELi was created by researchers at The Saban Research Institute of Children’s Hospital Los Angeles using liver organoid units – tiny, functioning versions of the complete organ – that were developed from both human and mice adult stem cells and progenitor cells. These were then implanted into mouse models with a biodegradable scaffold to help them grow.
Both the human and mice liver organoid units successfully developed into TELi, complete with the key cell types required for successful liver function. This included bile ducts, blood vessels, hepatocytes (liver cells), stellate cells and endothelial cells, although these were organised differently to a natural liver, making the research a significant step towards growing complete human livers.
The liver has been a key target of regenerative medicine over the last few years, with the Methuselah Foundation currently offering the $1m New Organ Liver Prize to the first team to regenerate or bioengineer a liver for that can successfully function in a large animal for 90 days.
The liver is considered one of the easier organs to attempt to generate, however that has not prevented researchers from running into significant problems during their efforts. Research using human-induced pluripotent stem cells, for example, has so far failed to produce hepatocytes-generating tissue, despite hopes in this area.
However, the researchers in this study had already demonstrated the success of their approach using other tissue types, and so decided to re-apply it to the liver.
“Based on the success in my lab generating tissue-engineered intestine and other cell types, we hypothesized that by modifying the protocol used to generate intestine, we would be able to develop liver organoid units that could generate functional tissue-engineered liver when transplanted,” said co-lead author and paediatric surgeon Dr Tracy C Grikscheit, a researcher at The Saban Research Institute of CHLA and associate professor of surgery at the Keck School of Medicine, USC.
And they were successful: hepatocytes proliferated in the tissue-engineered liver; the human liver demonstrated evidence of successful function in the mouse model and in a separate mouse model of liver failure the TELi provided some liver function.
The research, which also involved scientists from UCLA’s David Geffen School of Medicine and was published today in the journal Stem Cells Translational Medicine, is extremely promising for the development of a cell-based therapy for liver disease.
“A cellular therapy for liver disease would be a game-changer for many patients, particularly children with metabolic disorders,” said study co-author and paediatric surgeon Dr Kasper S Wang, a researcher at The Saban Research Institute of CHLA, associate professor of surgery at the Keck School of Medicine, USC and principal investigator for the Childhood Liver Disease Research and Educational Network.
“By demonstrating the ability to generate hepatocytes comparable to those in native liver, and to show that these cells are functional and proliferative, we’ve moved one step closer to that goal.”