Disparate Liver Biotechnologies

Advances in medical biotechnology happen constantly, and every field that is working towards long-term goals - such as, say, growing new organs from scratch or gaining sufficiently control over cells to repair and rejuvenate organs in situ - spins off new and incrementally better applications at each waypoint on the road. Every narrow field of applied life sciences has it's aura of new technologies and partial implementations.

So for the liver: one end goal would be the ability to simply grow livers on demand from a patient's own cells, another to reliabily trigger liver regrowth to the same degree as happens in lower animals. Still another is to repair damage and dysfunction globally in the liver's cells, so as to restore it to youthful capacity and function. The foundations for all of these goals are under construction, and along the way we see all sorts of interesting practical applications of biotechnology.

Here are a few such appications from recent news releases, with an emphasis on integration of biology with machinery, something that we'll be seeing a lot more of in the years ahead. These are first steps along a road that will see part-machine-part-biological tissues competing with artificially grown but otherwise wholly biological tissues, until such time as that distinction begins to blur at the edges with the advent of advanced forms of molecular nanotechnology.

Machine that preserves liver outside body offers new hope to transplant patients

At present, donated livers are cooled to 4C (39.2F) to preserve them, but this process does not stop them from deteriorating and they can only be stored for about 12 hours. The machine developed by scientists at Oxford University warms the organ to body temperature and circulates a combination of blood, oxygen and nutrients through it, allowing it to function just as it would inside a human body.

Researchers are confident they will be able to keep donor organs alive for 24 hours, and pre-clinical tests suggest it may be possible to preserve them for 72 hours or more. Modified versions of the portable device, which is the size of a supermarket shopping trolley, could also help transplants of other organs, including the pancreas, kidneys and lungs, and could be used to test the toxicity of new medicines.

Artificial human livers engineered for drug testing and discovery

Researchers have now made it possible for companies to predict the toxicity of new drugs earlier, potentially speeding up the drug development process and reducing the cost of manufacturing. The tool they have engineered to enable this is an artificial human liver piece, which mimics the natural tissue environment closely.

[These] liver tissue models for drug toxicity testing [consist of a ] three-dimensional porous scaffold that enables liver cells to spontaneously assemble into three-dimensional liver spheroids. These spheroids strongly resemble liver tissue. [By] seeding liver cells within a microfluidic system, the micro device is used to screen the liver's capacity to process different drugs and other compounds.

Using [a] microfabricated microporous membrane, the liver cells are sandwiched between the membranes, which can control the transfer of drugs, nutrients and oxygen to the cells, and provide more reliable and reproducible screening results. The membrane surface has been engineered to simulate liver cell interaction with [the extracellular matrix] and promote formation of liver tissues after the cells are seeded. Experiments have shown that the microporous membranes can maintain long-term liver cell functions for more than two weeks and will be useful for chronic liver toxicity testing, and industry-scale drug screening.

Team first to grow liver stem cells in culture, demonstrate therapeutic benefit

In a previous [study], investigators [were] the first to identify stem cells in the small intestine and colon by observing the expression of the adult stem cell marker Lgr5 and growth in response to a growth factor called Wnt. They also hypothesized that the unique expression pattern of Lgr5 could mark stem cells in other adult tissues, including the liver, an organ for which stem cell identification remained elusive.

[Researchers] used a modified version of [this method] and discovered that Wnt-induced Lgr5 expression not only marks stem cell production in the liver, but it also defines a class of stem cells that become active when the liver is damaged. The scientists were able to grow these liver stem cells exponentially in a dish - an accomplishment never before achieved - and then transplant them in a specially designed mouse model of liver disease, where they continued to grow and show a modest therapeutic effect. "We were able to massively expand the liver cells and subsequently convert them to hepatocytes at a modest percentage. Going forward, we will enlist other growth factors and conditions to improve that percentage. Liver stem cell therapy for chronic liver disease in humans is coming."

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