"planting" the liver! MIT led the three universities to plant human liver, successfully proliferating 50 times in mice

Release date: 2017-07-21

Maybe you don't know that the most industrious and exhausting organ in your body is it - the liver. Although it weighs only about 2 kilograms, its role is crucial. It removes toxins, stores glycogen, secretes proteins, and it works, but if one day it strikes?

Many diseases, such as cirrhosis and hepatitis, can cause liver failure. According to estimates by the World Health Organization, by 2030, the number of chronic hepatitis deaths in China can reach 10 million - hepatitis, which has become a "silent epidemic."

Currently, there are an estimated 90 million patients with chronic hepatitis B in China, of which 28 million need treatment and 7 million need urgent treatment for serious liver disease and cancer risk. There are about 10 million people infected with chronic hepatitis C in China, of which 2.5 million are in urgent need of treatment. Compared with the huge demand for liver disease patients, the number of donor livers can be said to be minimal.

Despite the powerful regenerative function of the liver, the risk of living donor liver transplantation cannot be ignored. There are already cases of death of donors worldwide, and patients undergoing liver transplantation are often accompanied by certain immune rejection.

In order to solve the shortage of donors, MIT, Rockefeller University and Boston University collaborated to embed three kinds of cells in biodegradable scaffolds to synthesize the basic unit of "artificial liver". After the "artificial liver" small unit was "planted" into the abdomen of a liver-impaired mouse, this small unit was expanded up to 50 times and fully functional with normal liver tissue! The study was published in the July 19 issue of Science, Science Translational Medicine.

Currently, the initial cells of the transplant in this study are mainly from human livers that have been refrigerated for too long and are not suitable for transplantation. Researchers are also exploring the best source of initial cells for the transplant. Other possibilities include extracting cells from the patient's own liver and eventually re-implanting the patient, which will avoid strong rejection. Hepatocytes produced by induced pluripotent stem cells will also be one of the pathways.

Figure 丨 Formation of lobular microstructure of "artificial liver"

"Organs are always in short supply. Our goal is to use this technology one day to help patients with organ transplants." One of the researchers in this experiment, Professor of Electrical Engineering and Computer Science at the Massachusetts Institute of Technology, Institute of Medical Engineering and Scientific Research. Professor Sangeeta Bhatia said.

This is not only the gospel of patients with severe liver disease, it is a great news for many patients with chronic liver disease, because in general, these patients are not eligible for liver transplantation.

"These patients with chronic liver disease will never be candidates for transplant surgery, but they are also suffering from liver disease. For this group of people, if you have a small "artificial liver" to assist liver function, imagine this will How exciting it is!"

Figure | Sangeeta Bhatia, Professor of the Department of Electrical Engineering and Computer Science at the Massachusetts Institute of Technology, Professor of the Institute of Medical Engineering and Science, MIT

Liver regeneration

In fact, current research on implantable livers is based on previous work at Bhatia Laboratories. She improved the shape and size of the stent to make it easier to implant in the abdomen of mice. Implanted hepatocytes can receive blood supply in mice, participate in the circulatory system, and exercise normal liver function.

However, these implanted "artificial livers" have fewer than 1 million hepatic parenchymal cells (cells that perform critical functions in the liver). A healthy human liver has about 100 billion hepatocytes, and Bhatia believes that if this amount is 10-30%, patients with liver disease will be saved.

In order to increase the number of liver parenchymal cells, the researchers decided to use a key feature of the liver - regeneration. "The liver is the only organ that can be regenerated. What's more, the liver can divide through mature cells without the need for other stem cells to participate," Bhatia said.

The establishment of the "artificial liver" inoculation system

Bhatia's team worked with Professor Christopher Chen of Boston University to design a basic unit of "artificial liver" consisting of hepatocytes, fibroblasts, and endothelial cells.

First, they combined the hepatocytes with fibroblasts to form globular organoids, and then designed the endothelial cells into a bundle-like structure, and the two structures were combined into fibrin according to certain rules. Once implanted into the mouse, the "artificial liver" unit will receive signal stimulation in the surrounding environment for regeneration - endothelial cells produce blood vessels, and the liver parenchyma cells regenerate and proliferate. After 11 weeks, the "artificial liver" is finally expanded. Increased by 50 times!

"The idea is like you are planting organs," Bhatia said. "What's really exciting is that the regenerative tissue is very similar to the body's liver structure."

So, the next question is, are these class organs invisible?

full functioning

In this question, the researchers collaborated with Charles Rice, a professor of virology from Rockefeller University, to implant "artificial liver" into mice with tyrosinemia and use it to induce liver repair. The drug is processed. (Tyrosinemia is a disease caused by abnormal tyrosine metabolism. Chronic patients can cause liver fibrosis, cirrhosis and even liver cancer. The only effective treatment is the early liver transplantation.) As the researchers hope, The mouse produces a liver regeneration signal. Of course, this is also the phenomenon that researchers hope to see in human trials in the future.

The liver has hundreds of functions throughout the human body, most of which are related to the regulation of metabolism, the detoxification of harmful substances, and the production of bile. Tests have shown that the transplanted human liver has all the functions of the above examples in the host mouse.

Figure 丨 Healthy liver and cirrhosis

“This work is very creative,” said Inder Verma, a professor of molecular biology from the Salk Institute, who spoke highly of the study. “Only a combination of primary hepatocytes, endothelial cells and stromal cells. It will eventually complete 50 times of amplification, which is really eye-catching, and also provides ideas for other organ-like cultures."

More interestingly, the researchers also found that after transplantation, the artificial liver even began to form small bile duct precursors, knowing that this is not their design. "Our next step will be to see how this is formed, whether it can be made faster and more orderly, and whether they are functional," Bhatia said.

The old saying goes: plant melons and melons. It seems that "the liver is liver" does not seem to be far away. A cell in the patient's body can generate a desired organ. The emergence and application of the future "artificial liver" will fundamentally solve the problem of donor shortage. Patients with liver disease will no longer need to wait indefinitely.

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references

Http://news.mit.edu/2017/engineered-liver-tissue-expands-after-transplant-0719

Http://stm.sciencemag.org/content/9/399/eaah5505

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Source: DeepTech Deep Technology (micro signal mit-tr)