Artificial liver grows after transplant

Liver cells transplanted into adipose tissue are trying to become a real liver

Kirill Stasevich, "Science and Life"

Liver diseases sometimes bring the patient to the point that the liver needs to be transplanted. But there are usually not enough donor organs for everyone. Is there any way to help a person whose liver is almost completely out of order, without having to completely transplant it? Is there any way to restore the liver right on the spot, in the patient's body?

It is about this method that researchers from MIT in its article in Science Translational Medicine (Stevens el al., In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease). Clinical trials are still far away here, but preliminary experiments on mice, as they say, inspire hope. 

A few years ago, Sangeeta N. Bhatia's laboratory developed a method by which additional hepatocytes (liver cells) could be transplanted into the body: they were planted on a special structure made of glass with hydrocarbon fibers; then this structure, the size of a contact lens, was transplanted into the abdominal cavity of mice. The cells quickly connected to the blood supply and began to work like a normal liver. 

However, such implants could hold no more than a million hepatocytes. And the human liver consists of 100 billion hepatocytes (not counting auxiliary cells), and in order to really help a patient with a diseased liver, he needs to transplant 10-30% of these billions. 

It is not possible to introduce such a cellular landing at the same time. However, the liver has one feature – it is able to renew itself without the help of stem cells (although it also has such cells); that is, adult, specialized hepatocytes retain the ability to divide. So, we can actually transplant a few cells, hoping that they themselves will make up for the lack. You just need to transplant them so that they continue to multiply. 

Employees of Sanjita Bhatia and their colleagues from several scientific centers in the USA collected microcomplexes from liver cells, which were planted in the thickness of a protein biodegradable gel. The cell complexes included human liver cells, connective tissue fibroblasts, which serve as auxiliary cells in tissues, and umbilical vein epithelial cells – they were supposed to form blood vessels.

Drawings from an article in Science Translational Medicine – VM.

The gel with the cells was transplanted into adipose tissue in mice, and after some time it turned out that the transplanted liver tissue increased by 50 times. 

The mice that were experimented with had a genetic defect – some amino acid metabolism reactions did not work for them, and toxic substances accumulated in the body; in addition, the animals had to take medications to survive. Under the influence of toxins and drugs, the mice's own liver secreted molecules that signaled that there was something wrong with it – and these molecules, reaching the transplanted cell complexes, stimulated the growth of new blood vessels, and those, in turn, prompted the transplanted hepatocytes to divide. 

The authors of the work note that the most successful in this sense were those complexes in which the cells were not just mixed in a spherical cell, but in which the cells for the vessels lay on top of the hepatocytes – then structures resembling the architecture of the hepatic ducts appeared in the growing tissue. 

Such pieces of liver also synthesized albumin and transferrin – that is, those proteins that liver cells should normally synthesize. In general, the "artificial liver" performed all its functions, from detoxification to the production of bile. That is, the liver tissue not only grew in size, but also tried – and very unsuccessfully – to become a real liver. 

Perhaps in the future, in patients with liver problems, it will be possible to grow a new liver right in the body in this way – even if not entirely, even if at least half or a third, but this will be enough. Although, of course, before it comes to clinical trials, many more questions will need to be solved, for example, where is it better to transplant "liver seeds" and where to get cells for transplantation – from a ready-made liver or to get them using stem technologies from the patient's own cells. 

Similar studies, by the way, are carried out with insulin cells, which after transplantation should replace their colleagues who died due to type I diabetes. So, in May, we wrote about the experiments of employees from the Institute of Diabetes at the University of Miami, who successfully transplanted donor pancreatic cells onto the omentum – this type of operation allows to reduce inflammatory complications. 

Portal "Eternal youth" http://vechnayamolodost.ru  21.07.2017