Liver Organoids Come Ever Closer to Natural Liver Tissue

Tissue engineers continue to improve the quality of their creations. The liver is one of the easier organs to work with, given the much greater regenerative capacity of liver cells. It is, nonetheless, an organ with a complex small-scale internal structure, and getting that right is a process of incremental advances. The tissues created via present state of the art approaches are usually still small, lacking the capillary networks needed to support tissue larger than a few millimeters in depth. The only way to provide those networks is to use decellularized donor organs, the cells destroyed, and the organ thus reduced to the scaffold of the extracellular matrix, complete with blood vessels and chemical cues. If the starting point is a cell sample without such a scaffold, blood vessels remain a challenge. By the time that challenge is reliably solved, however, it seems likely that the research community will be ready to build fairly accurate replicas of at least a couple of different real organs, even without donor tissue to provide a scaffold.

The creation of living mini-organs is a relatively new area of science with the potential to replace animal models that are not always accurate. The liver organoids, made with human cells, are less than one-third inch in diameter. While scientists have already created liver organoids to screen new drugs for liver toxicity, the livers developed in this research represent several "firsts" in the quest to build a functional model of human liver development. To make the organoids, scientists allow fetal liver progenitor cells, an immature cell that is destined to become a specialized liver cell, to self-assemble on a small disc. The discs are made of ferret liver that has been processed to remove all of the animal's cells. The resulting organoids, which assemble within two to three weeks, are the first to model actual human liver development.

The research is significant in two ways. First, the scientists showed that these organoids generated hepatocytes, the main functional cells of the liver. This achievement represents a milestone in work to create truly functional bioengineered liver tissue for transplantation into patients. Second, while other scientists have shown that lab-grown livers can generate bile ducts, this is the first study to show the stepwise maturation of bile ducts exactly as can be observed in the human fetal liver. Bile ducts carry bile, a fluid that is secreted by the liver and collected in the gall bladder to digest fats.



Unrelated, but has anyone here watched Black Mirror? It's a sci-fi series exploring the impact of future technology on everyday life. Very good, in general. Something amusing I the episode 'Arkangel', there's a character - the protagonist's father - who claims to be 2000 years old. Plausible enough - except that it implies that the episode takes places approx 2000 years in the future. And NOTHING else has changed. There are still cars, there are still roads, children still go to school, teenagers snort cocaine for entertainment, human bodies still look exactly the same. I'm sure some of it was due to budget constraints - you'd need Avatar levels of CGI to show what the future will actually look like - but I found it funny regardless. Even in one of the only shows to tackle futurist ideas seriously, people still struggle to envision the magnitude of the changes to come.

Posted by: TL at February 14th, 2018 9:23 AM

Do we actually need to generate a complete organ; is there any way we could 'seed' an old and damaged liver, say, with lots of these organoids, and have them join and regenerate the existing tissue (therefore taking advantage of the blood supply already in place)?

Posted by: Mark at February 14th, 2018 9:27 AM

@Mark: I don't know the answer to this question. I donated a smaller amount to WAKE Regenerative Medicine. If millions donated $ 100 or maybe only $ 10 this research would accelerate.

Posted by: Norse at February 14th, 2018 10:06 AM

I thought some scientists had denatured the vascular structure (xylem, phloem) of the leaves of Elephant Ear plants and used it as scaffolding for tissue growth.

Posted by: Tom Schaefer at February 14th, 2018 11:46 AM
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