A billion liver cells can be made from 1 liter of fat
Liver made of fat
Scientists used liposuction waste for liver regenerationNadezhda Markina, <url>
At the same time, they avoided the risk of the formation of cancerous tumors. True, all this is still applicable to mice, but there is hope for the early application of similar technology for humans.
Stanford University scientists have found a new way to regenerate the liver, which they have so far tested on mice. They used non–embryonic cells and non-induced pluripotent cells as raw materials for the production of liver cells - hepatocytes. They took human adipose tissue cells, which were waste from liposuction. And turned them into fat in the mouse body.
The researchers described the results of the experiment in the journal Cell Transplantation (the content of the work is retold in the press release of Stanford School of Medicine: Researchers demonstrate an efficient method for converting fat cells to liver cells - VM).
The technique used by Stanford specialists has one very important advantage. If hepatocytes are grown from embryonic stem cells or from cells that have been regained pluripotency by genetic manipulation – the ability to differentiate into cells of different tissues, there is always a risk of not coping with this pluripotency. There is a possibility that the transplanted cells will develop into a cancerous tumor, and this is the biggest risk that slows down this technology. But if hepatocytes are obtained from mature (fat) cells, bypassing the pluripotency stage, then there is no risk.
The liver is distinguished by the fact that even in humans it is endowed with high regeneration abilities. Part of the liver can grow into an entire organ. But the regenerative ability of the liver may be lost due to chronic alcoholism, hepatitis or toxicological lesions.
As Professor Gary Peltz emphasizes, all elements of the technology of converting fat into liver cells can be adapted to humans. The whole process takes nine days, and this is enough to start the regeneration process. Otherwise, the patient will not survive without liver transplantation.
The state of liver transplantation can be judged by the following figures: about 6,300 transplants are performed annually in the United States, and about 16 thousand people are on the waiting list. From this list, more than 1,400 people die every year without waiting for an organ. In addition, liver transplantation is associated with risk and is complicated by lifelong use of immunosuppressive drugs to avoid organ rejection.
"We believe that our method may be suitable for the clinic," says Peltz, "and since the new liver tissue will be obtained from the patient's own cells, we expect that after the procedure he will not need immunosuppressants."
The method by which it is possible to transform stem cells from fat (adipose) into liver cells was discovered by Japanese scientists in 2006. This is chemical stimulation. But, firstly, it takes quite a long time, for 30 days, and secondly, this method is not effective enough (the proportion of cells transformed into hepatocytes is only 12%) and does not allow to obtain a sufficient number of cells for liver reconstruction.
Stanford researchers have developed an alternative technology they call spherical cultivation. It allowed to obtain hepatocytes within 9 days, and the conversion efficiency was 37%. These results were achieved at the time of publication, but since then, according to Peltz, it has been possible to achieve 50 percent efficiency in 7 days.
Xu Deng, the first author of the article, took the technology of spherical cultivation from previous work with embryonic stem cells. He cultured stem cells from fat cells not on the flat surface of a Petri dish, but in a liquid, where they formed spherical clusters. Having accumulated a sufficient number of cells, the researchers injected them into mice with suppressed immune systems (so that human cells would not be rejected). In addition, these mice were genetically modified in such a way that a certain substance caused them rapid and fatal toxic liver damage.
These mice were injected with 5 million received human hepatocytes. Four weeks later, the researchers performed a blood test on the mice and made sure that human hepatocytes produce human albumin, which is contained in the plasma of mouse blood.
In the next four weeks, the amount of this protein tripled. Scientists consider this a very good result, since in previous experiments with growing human liver in mice, the content of human albumin was minimal. The blood test also showed that the "humanized" liver of mice is able to filter blood, purifying it from toxins.
The transplanted cells have integrated into the organ and express biochemical markers of mature human hepatocytes on their surface. They also formed the multicellular structures necessary for the formation of the bile duct.
Two months after the cell transplant, the mice showed no signs of cancerous tumors forming. At the same time, mice transplanted with hepatocytes derived from induced pluripotent stem cells formed multiple tumors.
The human liver weighs 1.5 kilograms, which is 800 times more than the mouse liver, and contains about 200 billion cells. So when adapting the technology to a person, it is necessary to solve the problem of obtaining such a number of cells. According to the researchers, about a billion cells can be obtained from 1 liter of fat pumped out during a single liposuction operation. But since cells will multiply in the body, eventually their number will reach 100 billion, and this is enough for regeneration. This procedure can replace the transplantation of a donor liver.
Now scientists are adapting their technology to test it on large animals. They expect to prepare for clinical trials in two to three years.
Portal "Eternal youth" http://vechnayamolodost.ru22.10.2013