Chinese scientists have designed a "new bioartificial liver system"

Chinese scientists have designed a "new bioartificial liver system"

January 19, 2016 Source: Bio Valley

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It can significantly improve the survival rate of liver failure pigs and is expected to continue the life of patients with liver failure. The relevant results were published on January 16th in the internationally renowned academic journal Cell Research.

At the beginning of the year, the team had launched the first clinical treatment of “hiHep cells” bioartificial liver, successfully treating a patient with liver failure. In 2016, the team will conduct further clinical research in Shanghai and its surrounding areas.

For severe liver failure, in addition to liver transplantation, there is currently no effective treatment. In response, scientists have proposed a treatment using a bioartificial liver system to provide liver function to patients. Bioartificial liver is an external liver function support system that can promote the recovery of autologous liver function in patients with liver failure. It can also gain time for patients planning liver transplantation and wait for a suitable liver source.

The core technology of bioartificial liver is functional hepatocytes for treatment. At present, bioartificial liver developed at home and abroad mainly uses porcine primary hepatocytes or human hepatoma cells as a source of functional hepatocytes. However, these cells have large defects in safety or in terms of functionality, which seriously depresses the clinical application of bioartificial liver. Therefore, obtaining new functional liver cells is a key step in promoting the clinical application of bioartificial liver.

In this study, scientists filled "hiHep cells" into bioartificial liver and observed their treatment of pigs with acute liver failure. The experimental results show that untreated acute liver failure pigs generally die in about 3 days, while the survival rate of acute liver failure pigs treated with "hiHep cells" bioartificial liver is 80%. After survival, the pig's indicators gradually returned to normal levels.

According to researcher Hui Lijian, the liver is similar to a "chemical plant", which itself has the functions of biosynthesis and metabolic detoxification. If the liver cells have been depleted, in the case of almost loss of these functions, the doctor can participate in the normal liver function activities of the human body by means of some foreign liver cells, which can help the patient to go through an extremely difficult and dangerous period. This study demonstrates for the first time that the bio-artificial liver system based on “hiHep cells” is effective and safe in large animal treatment experiments, which provides a solid foundation for further clinical research in the next step.

At present, China has become the world's most socially costly country for hepatitis B, cirrhosis and liver cancer. Experts predict that the research results of the new bioartificial liver system are expected to significantly improve the survival time of patients, and strive for more rescue time for liver treatment and liver replacement.

Under the special support of the stem cell pilot of the Chinese Academy of Sciences, the research team successfully treated acute liver failure pigs based on human functional hepatocytes, hiHep cells, using a bioartificial liver system. At the same time, through this system, they also carried out the first clinical treatment experiment, allowing patients with a history of hepatitis B for more than 40 years and recent liver failure to turn to safety. Yesterday, the internationally renowned academic journal Cell Research published relevant results online. For severe liver failure, in addition to liver transplantation, there is no clear treatment. Bioartificial liver is a liver function support system derived from in vitro and plasma circulation. It can promote the recovery of autologous liver function in patients with liver failure. It can also save valuable life time for patients planning liver transplantation and wait for a suitable liver source. Currently, the core technology of bioartificial liver is to obtain functional hepatocytes for treatment.

In 2011, the Huilijian team of the Shanghai Academy of Sciences of the Chinese Academy of Sciences successfully formed the liver cells of mouse skin cells through transformation and differentiation. The results were published in the international authoritative academic journal Nature, and won the honor of “Top Ten Progress in Chinese Science”. . In 2014, the Huilijian team re-programmed human “fibroblasts” into hiHep cells. The article was published in the internationally renowned journal “Cell Stem Cells” and was named “2014 China Annual Paper” by Cell Publishers.

The internationally renowned academic journal Cell Research published online the research team of the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, and the team of Ding Yitao of the Affiliated Drum Tower Hospital of Nanjing University, and the Pan Guoyu team of the Chinese Academy of Sciences. The latest achievements of Zhou Yan team of East China University of Science and Technology. The study used hiHep cell-based bioartificial liver system to treat acute liver failure pigs, which significantly improved the survival rate of liver failure pigs and proved the possibility of clinical application of hiHep cells.

For severe liver failure, in addition to liver transplantation, there is currently no effective treatment. In response, scientists have proposed a treatment using a bioartificial liver system to provide liver function to patients. Bioartificial liver is an extracorporeal liver function support system that can promote the recovery of autologous liver function in patients with liver failure, and can also gain time for patients planning liver transplantation, waiting for a suitable liver source. The core technology of bioartificial liver is functional hepatocytes for treatment. At present, the bioartificial liver developed at home and abroad mainly uses porcine primary hepatocytes or human hepatoma cells as a source of functional hepatocytes, but these cells have great defects in safety and function, and the bioartificial liver is inhibited in clinical application. Therefore, obtaining new functional liver cells is a key step in promoting clinical application of bioartificial liver.

In 2011, the Huilijian team successfully transfected mouse skin cells into hepatocytes and published them in the world's leading academic journal Nature, which achieved the top ten progress of Chinese science in that year. In 2014, the Huilijian team successfully transduce human fibroblasts into functional hepatocytes (hiHep cells). The article was published in the internationally renowned academic journal Cell Stem Cell and was named “2014 China Annual Paper” by the Cell Publishing House. On this basis, in order to further promote the transformation of hiHep cells into clinical applications, the Shanghai Institute of Biochemistry and Cell Research of the Chinese Academy of Sciences and the Nanjing University Affiliated Drum Tower Hospital, the Chinese Academy of Sciences Institute of Medicine, East China University of Science and Technology and other units will cooperate fully and will expand on a large scale. hiHep cells are combined with a bioartificial liver system for the treatment of large mammals suffering from acute liver failure.

In this study, the scientists performed a large number of functional optimization enhancements on hiHep cells, successfully amplifying them to the number of clinical treatment orders, and filling them into bioartificial liver for the treatment of acute liver failure pigs. Untreated acute liver failure pigs usually die in about 3 days, while the survival rate of acute liver failure treated with bio-artificial liver using hiHep cells is 80%. After survival, the physiological indexes of the pigs gradually returned to normal levels. This study demonstrates for the first time that hiHep cells generated by transdifferentiation can be applied to bioartificial liver systems. The transformation of biomedical basic scientific research results into clinical application is a hotspot in the current scientific and technological circles and industry. The success of large animal treatment experiments based on hiHep cells in bioartificial liver system has initially proved its effectiveness and safety, and it is also the next step for comprehensive development. Clinical research has laid a solid foundation.

At the beginning of this year, through the joint efforts of scientists, the first clinical treatment experiment of bio-artificial liver system based on hiHep cells was completed. A patient with a history of hepatitis B with more than 40 years of history and recent liver failure was treated. The patients received various medical treatments in the early stage without obvious improvement. After the hiHep bioartificial liver treatment, the liver function indexes of the patients recovered well and passed the dangerous period. This clinical case is a solid and powerful step in the clinical application of hiHep bioartificial liver.

60-year-old woman's liver failure is hanging on the front line. What if there is no liver source? A few days ago, experts from the Nanjing Gulou Hospital extracted the seed cells from human fat and programmed them into hiHep cells to make "artificial liver". They successfully pulled the dying lady Ms. It is understood that the new bio-artificial liver support system using human hiHep cells is the first time in China.

Suffering from hepatitis B for 40 years, women with liver failure

Ms. Zhong, 60, has hepatitis B for more than 40 years. She has had urine yellow, yellow skin and yellow eyes many times. Every time she uses drugs to protect her liver, and she stops taking it after getting better. Seven years ago, Ms. Zhong examined cirrhosis; in September last year, esophageal varices bleeding occurred, and spleen resection + combined devascularization was performed at Nanjing Gulou Hospital, and the postoperative recovery was good.

In December last year, the patient again showed generalized weakness, edema, and yellow urine. Biochemical examination showed persistent increase in liver transaminases and bilirubin. He was diagnosed with liver failure, and his effect was not satisfactory after various medical treatments. His life was dying. After thorough and meticulous communication with the family members of the patient, Prof. Ding Yitao, professor of general surgery at the Affiliated Drum Tower Hospital of Nanjing University Medical College, and Professor Shi Xiaolei and Deputy Director of General Surgery, Professor Wu Yafu decided to adopt the new bioartificial based on human hiHep cells independently developed by Drum Tower Hospital. The liver support system" treats patients.

"In vitro artificial small liver" on behalf of the liver "life-saving"

It is understood that the so-called artificial liver is actually a set of extracorporeal circulation system, which replaces the human liver to perform liver function, metabolism, detoxification, and synthesis of blood coagulation factors. “Simply speaking, it is an in vitro artificial small liver that works in the short term instead of the liver.”

Professor Ding Yitao said that liver transplantation is the most effective method for treating liver failure. However, due to shortage of donor organs, matching, etc., only a small number of patients can receive liver transplantation in time, and most patients are waiting to die. The bioartificial liver support system creates conditions for hepatocyte regeneration and liver function recovery, making this part of the patient waiting for a liver transplant.

After three hours of treatment, Ms. Zhong actually got out of bed, she told the doctor that she was full of strength, and the examination also found that the patient's high transaminase rapidly improved and the blood coagulation function recovered. It is understood that this is the first bio-artificial liver support system based on human hiHep cells in China.

Fat cells make artificial liver, saving women's lives

Ding Yitao told reporters that the human artificial liver based on human hiHep cells is the third generation of artificial liver researched by them. Since 1998, the first and second generation bioartificial livers have been developed. Compared with the first-generation and second-generation bioartificial livers, liver cells were used to cure liver disease, and the third generation was improved by extracting liver cells from human body fat and blood. Since the cells are human-derived, immune rejection can be avoided during cell transplantation, and it is more easily accepted by patients, which is conducive to clinical transformation. The key to this process is the hiHep cells. When treating for Ms. Zhong, the expert extracted the cells from a healthy person's fat cells and reprogrammed them into hiHep cells, successfully pulling the dying lady Ms.

Drum Tower Hospital, more than 100 people a day transplant liver transplantation

Wu Yafu said that there are more than 100 people waiting for the liver transplant in the liver and gallbladder transplantation center of the Drum Tower Hospital every day. However, only 30 people were lucky enough to wait for the donor liver and accepted the transplant last year. "The use of bio-artificial liver support system is actually creating more opportunities for patients with liver failure waiting for transplantation. Some people even get a rebirth during the waiting process." Wu Yafu told reporters that the liver is responsible for the related functions by bioartificial After the liver support system is “shouldered”, the liver that is “sorrowful and on the verge of stopping” will be rested and restored. At this time, good liver cells will be regenerated in “cultivation”. It is understood that treatment requires one or two thousand yuan.

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