Xenotransation entered into the age of clinical research. Research teams at the University of Maryland Medical College performed the heart transplantation of the pig and scientists at both Massachusetts General Hospital and New York University who recently implanted kidneys from pig to human beings3and4and5and67. Scientists from the University of Pennsylvania used pigs for the treatment12. The current study was conducted to evaluate the feasibility of liver transplantation from pig to the liver. The use of genetic modification and specific environment free from pathogenic factors may have prevented acute and potential PRV rejection, PCMV or other swine virus infections in the recipient.
As shown, heterogeneous auxiliary liver transplants were performed. To ensure the best match, the caliber and flow speed of the main blood vessels are evaluated and received before surgery. This guarantees adequate blood in the taste of Xenograft and the stability of the blood circulation in the recipient, and avoid the weak graft caused by dynamic disorders, as stated in the reference. 6. Additional liver transplantation is an ideal treatment for the bridge for individuals with liver failure, because it is not difficult to remove the pinear and rebuild IVC when restoring the original liver function or when a suitable donor liver is available. We removed the taste of Xenograft and we rebuild IVC at the end of the study to simulate the aforementioned situation. Moreover, the heterogeneous liver transplant protocol has improved the efficiency of interventional clotting directly from the deep vein of the lower end. The first case of the pig to the heart found the parts of the pigs to the heart in the terminal fabrications7. Likewise, the current study found that D-DIMER levels were highly transient after surgery (extended data 5a). Then the decay of the thrombosis was used in time to keep the Xenograft function.
In fact, the flow in IVC Infrarenal is not physiological. To achieve physiological dynamics, we must perform partial partial liver transplantation. However, this will remove part of the original liver and may cause possible complications such as liver malfunction, yellow leakage or bleeding in patients. Because our goal is to help patients with acute liver failure during the critical period, there is no need to perform a transplant that is completely compatible with physiology. As long as Xenograft can provide metabolism and clotting functions for a certain period, this planting is sufficient. In this study, we used blood flow in IVC to supply Xenograft, which successfully returned to the heart. Throughout the entire study, no edema was noticed in the lower extremities, indicating that the circulation of the lower limb is guaranteed. More importantly, the taste of Xenograft remained functional and the blood dynamics remained stable until the completion of the study. Therefore, the non -physiological flow in this study did not cause severe disturbance.
Severe rejection is one of the most important issues in planting Xenotransion in pre -clinical models18. Fortunately, no evidence of very whale rejection was found in the current study. In addition to the release of the α-galactosyltransferase gene, a series of immunosuppressive factors has been used, Tacrolimus (FK506) played a vital role. During the early stage of this mixture, we used Tacrolimus at a concentration of 5 mg−1 (The upper limit of normal), according to our previous protocol. However, the high blood concentration of Tycrolimus was observed on a post -surgery day 2, which may result from drug abuse of drug metabolism. We adjusted the dose in time. In the late stage of this experiment, the total bilirubin level was raised, which may be associated with the toxicity of the takrolimus.
Whether the use of Rituxan (Rituximab) during the identification immunity suppression is one of our discussion axis before surgery. Because of the huge benefits of genetic liberalization, mixed immunity no longer has a significant impact on the survival of the illegal gain. Therefore, Ritoxan was not included in the immunity strategy for liver transplantation19,20. Likewise, we did not use Ritoxan in our previous paths from planting pigs to pigs, because the B cells were not activated in these studies.13. Therefore, in this study, Ritoxan was not used at first. When the bacterium cells began to increase, we had to adopt Ritoxan, along with the exchange of plasma and the treatment of immunoglobulin intravenously, which can theoret the antibodies and plasma that were formed. This experiment indicates that the activation of the B cells may occur in planting liver from the pig to the pig. More investigations are needed before we can integrate Retoxan into our immunosuppressive strategy.
The contradiction in the quantities of Alt and AST was unexpected and something not noticed in previous animal studies. More importantly, an AST height was revealed during the early stage in transplantation from pigs to the heart that was conducted in a previous study6. It is reasonable that AST be launched with myocardial cells. This early increase in the quantities of creatine Kenaz and Cynatinine Kinaz-Myoskardial, which is observed at the same time point (7E-extended data). Consequently, the heart muscle damage should be evaluated in the early stage of liver transplantation and protect the pharmacological heart muscle that is implemented if necessary. It is worth noting that some yellow stagnation has been observed in the original liver tissues of the recipient on the 10th day, which may explain the high bilirubin that was subsequently observed. However, this was absent in xenograft. Thus, current therapeutic medications are likely to be a little less toxic to the liver than the human liver.
Not overcoming the clotting is the main cause of a dysfunction in xenograft21And it happened in the first percentage of the pig to the heart7 In our previous cases of planting pigs into the liver. However, no serious disorder in bleeding or coagulation occurred in the current state. PT remained relatively stable after surgery, APTT increased transient in the early stage and later decreased, PLT decreased transient in the early stage and increased later. Bleeding and blood clotting disorders were more moderate in this recipient that the brain passes through in the former monkey recipients, indicating that human genetic adjustments may work better in humans. Because of the advantages of heterogeneous auxiliary liver, we were able to intervene after the early height of D-DIMER and prevent potential photovoltaic blood clots.
Future studies will need to choose between the illegitimate gain bridge or the permanent position of wood cultivation. Although Xenograft can secrete bile and produce pigs in this study, it is unlikely that the production of bile and pigs albums is sufficient to support the human body for a long time. Thus, as shown in the reference. 17The current liver transplant methods may be more convenient as a treatment of an auxiliary bridge for individuals with liver failure waiting for the human liver. However, it will be important to designing liver transplant methods from pig to pig to the effective liver of future patients.
We admit the restrictions imposed on this study. First, at the request of the family members of the recipient, the study was completed on the 10th day, which made the follow -up period not sufficient to analyze the amendments in the national taste function over a long period. Second, at the present time, we can not only measure the basic functions of the liver, such as cessation of albumin and yellow secretion. However, this unique liver transplant from the pig to the liver can still plant important information that cannot be provided through animal experiments alone.