Scientists generate functional human tissue-engineered liver, bringing complete lab grown organs a step closer

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 scientists' newly grown liver tissue, right, next to a biodegradable scaffold. Image courtesy of The Saban Research Institute at Children's Hospital Los Angeles

The scientists’ newly grown liver tissue, right, next to a biodegradable scaffold. Image courtesy of The Saban Research Institute at Children’s Hospital Los Angeles

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.

A 3D rendering of a normal liver (left) and one with significant cirrhosis

A 3D rendering of a normal liver (left) and one with significant cirrhosis

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.”

New research claims a video game can improve doctors’ ability to recognise severe trauma in patients

New research has concluded a specifically-designed video game improves doctors’ ability to recognise when patients need to be transferred to a severe trauma centre.

The research, by the University of Pittsburgh School of Medicine and published today in the BMJ, revealed the game Night Shift was better at preparing doctors to recognise patients who needed higher levels of care than reading traditional educational materials.

This was the case even though doctors who were made to play the game, in which doctors play as a fictitious, young emergency physician treating severe trauma patients, enjoyed it less than those who were asked to read relevant materials.

“Physicians must make decisions quickly and with incomplete information. Each year, 30,000 preventable deaths occur after injury, in part because patients with severe injuries who initially present to non-trauma centres are not promptly transferred to a hospital that can provide appropriate care,” said the game’s creator Deepika Mohan, MD, MPH and assistant professor in Pitt’s departments of Critical Care Medicine and Surgery.

“An hour of playing the video game recalibrated physicians’ brains to such a degree that, six months later, they were still out-performing their peers in recognising severe trauma.”

Night Shift was designed by Mohan to tap into the part of the brain that uses pattern recognition and previous experience to make snap decisions by using subconscious mental shortcuts – a process called heuristics.

Doctors in non-trauma centres typically see only about one severe trauma per 1,000 patients. As a result, their heuristic abilities can become skewed toward obvious injuries such as gunshot wounds, and miss equally severe traumas such as internal injuries from falls.

On average, 70% of severely injured patients who present to non-trauma centres are under-triaged and not transferred to trauma centres as recommended by clinical practice.

“There are many reasons beyond the doctor’s heuristics as to why a severe trauma patient wouldn’t be transferred to a trauma centre, ranging from not having an ambulance available to a lack of proper diagnostic tools,” said Mohan.

“So, it is important to emphasize that recalibrating heuristics won’t completely solve the under-triage problem and that the problem isn’t entirely due to physicians’ diagnostic skills. But it’s heartening to know we’re on track to develop a game that shows promise at improving on current educational training.”

For the study, Mohan recruited 368 physicians from across the US who did not work at hospitals specialising in severe trauma. Half were assigned to play the game and half were asked to spend at least an hour reading the educational materials.

Participants then responded to questionnaires and completed a simulation that tested how often they “under-triaged,” or failed to send severe trauma patients to hospitals with the resources necessary to handle them.

Physicians who played the game under-triaged 53% of the time, compared with 64% for those who read the educational materials.

Six months later, Mohan reassessed the physicians and found that the effect of the game persisted, with those who played the game under-triaging 57% of the time, compared to 74% for those who had read the educational materials.

Multimedia courtesy of Schell Games.

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Source: Gizmodo

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Source: BBC

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Source: Inverse

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Source: BBC

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Source: Ars Technica

The maker of Budweiser beer reserves 40 Tesla electric trucks

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Source: Reuters