Ethical Issues and Resolutions in Human-animal Chimera Research / 中国医学伦理学

Human-animal chimera technology is increasingly applied to large animals. It is highly possible to cultivate human organs in pigs for transplantation in the future. Chimeric animals contain more and more human materials and are present in their brains and reproductive systems, which may humanize them and give them a higher moral status and even dignity. It raises an important ethical question: should such chimeric animals be created? If so, how they should be treated. It is not convincing to refute the research of human-animal chimera with the arguments of destroying natural order, unnatural and moral chaos. But the non-identity view holds that scientific research makes the lives of chimeric animals more valuable and that they are not actually harmed because their only other options do not exist. The answers to these ethical questions can resolve the ethical risks arising from the research of human-animal chimera.

Latest research and prospect of CD47 in kidney transplantation / 器官移植

CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.

Present situation and progress of xenotransplantation at home and abroad / 器官移植

Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

Research report of living donor kidney harvesting in Bama miniature pigs with six gene modified / 器官移植

Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.

Application of xenotransplantation in clinical practice / 器官移植

Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, organ shortage is a global problem, which limits further development of organ transplantation. Recent research shows that genetically modified pig may become a realistic alternative source of clinical organ transplantation donor. Xenotransplantation may serve as one of the effective measures to resolve the problem of organ shortage. Since 2021, 2 cases of living xenotransplantation and 6 cases of xenotransplantation in brain death recipients have been performed worldwide, and phase Ⅰ clinical trial of xenotransplantation has been launched, and the results have exceeded expectations. Therefore, in this article, recent clinical trial results of xenotransplantation in living and brain death recipients were retrospectively analyzed, and scientific, technical and ethical issues related to clinical research of xenotransplantation were illustrated, hoping to provide reference for clinical research of xenotransplantation in China and promote the development of xenotransplantation in clinical practice.

Construction and validation of a prediction model for public acceptance of kidney xenotransplantation in China / 器官移植

Objective To explore the public attitude towards kidney xenotransplantation in China by constructing and validating the prediction model based on xenotransplantation questionnaire. Methods A convenient sampling survey was conducted among the public in China with the platform of Wenjuanxing to analyze public acceptance of kidney xenotransplantation and influencing factors. Using random distribution method, all included questionnaires (n=2 280) were divided into the training and validation sets according to a ratio of 7:3. A prediction model was constructed and validated. Results A total of 2 280 questionnaires were included. The public acceptance rate of xenotransplantation was 71.3%. Multivariate analysis showed that gender, marital status, resident area, medical insurance coverage, religious belief, vegetarianism, awareness of kidney xenotransplantation and whether on the waiting list for kidney transplantation were the independent influencing factors for public acceptance of kidney xenotransplantation (all P<0.05). The area under the curve (AUC) of receiver operating characteristic (ROC) of the prediction model in the training set was 0.773, and 0.785 in the validation set. The calibration curves in the training and validation sets indicated that the prediction models yielded good prediction value. Decision curve analysis (DCA) suggested that the prediction efficiency of the model was high. Conclusions In China, public acceptance of kidney xenotransplantation is relatively high, whereas it remains to be significantly enhanced. The prediction model based on questionnaire survey has favorable prediction efficiency, which provides reference for subsequent research.

Progress in subclinical research of kidney xenotransplantation / 器官移植

Xenotransplantation is an efficient pathway to solve the problem of transplant organ source deficiency in clinical settings. With the increasing progress of gene editing technique and immune suppression regimen, important development has been achieved on researches regarding pig to non-human primate kidney xenotransplantation, which provides a good condition for the introduction of the technique in the clinical application. In view of the substantial difference between human and non-human primate, and to meet the needs of current ethic requirements, it is necessary to perform subclinical studies for pig to human kidney xenotransplantation. In recent years, such subclinical studies with regard to the genetically modified pig to brain death recipient kidney xenotransplantation had been performed, indicating that kidney xenotransplantation gradually began to transit to the clinical development stage. However, donor/recipient selection and immune suppression regimen has not reached a consensus yet, and has to be clarified in subclinical studies. In this article, the current status and confronted problems of donor/recipient selection, immune suppression regimen and post transplantation management in the subclinical studies of kidney xenotransplantation were reviewed, aiming to promote the clinical transformation of kidney xenotransplantation to the clinical application.

A Review on Pig-to-Human Organ Transplantation / 中国生物化学与分子生物学报

Xenotransplantation holds the promise of being used to address the imbalance between organ supply and demand for clinical transplantation. Pigs have natural features that make them more suitable donors for transplant organs than non-human primates. A series of biological barriers that arise after pig organ transplantation have been overcome by genetic engineering and pharmacological suppression. Mean- while, the gradual maturity of the genetic engineering technology has been significantly optimized for suit- able pigs for xenotransplantation, and promoted the development of pig organ transplantation research. Although it will take time for pig organ xenotransplantation to enter the clinical trial stage, recent studies conducted in a few brain-dead or critically ill patients have exhibited the great potential of porcine xeno- transplantation in solving the imbalance between supply and demand of organs for clinical transplantation.

Kidney xenotransplantation: status quo and development trend of physiological research / 器官移植

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

Research progress on the role of costimulatory signaling pathway in xenotransplantation / 器官移植

Organ shortage is a critical factor limiting the development of organ transplantation. Xenotransplantation is expected to resolve the problem of organ shortage, which has become a new research hotspot. Study of costimulatory signaling pathway related to T cell regulation is a hot topic in terms of immunity of xenotransplantation. Since the discovery of costimulatory molecule CD28, multiple costimulatory molecules have been identified, including costimulatory and coinhibitory receptors and their related ligands. Specific T cell activation of donors is the key factor leading to acute immune rejection. The expression and induction of costimulatory molecules on T cells differ during different immune stages, and these costimulatory molecules play a key role in maintaining T cell tolerance and the balance of T cell immune response. At present, increasing attention has been diverted to the role of costimulatory signaling pathway in organ transplantation. In this article, the latest research progress in costimulatory signaling pathway related to xenotransplantation immunity was reviewed, aiming to provide reference for the optimization of xenotransplantation immunosuppression regimen.

Trends in clinical islet transplantation / 中华器官移植杂志

Islet transplantation has developed rapidly over the last 20 years and is becoming one of the ideal clinical treatment options for type 1 diabetes mellitus (T1DM). There is growing clinical evidence that islet transplantation has significant efficacy in insulin independence or reduction, preventing hypoglycemic episodes and preventing diabetic complications.However, clinical islet transplantation still faces challenges, such as a shortage of donor resources, difficulties in early implantation and survival of islet grafts, and immune rejection.In the future, donor pancreatic donation and its effective utilization should be promoted, and clinical exploration of xenogeneic islet transplantation and stem cell-derived islet transplantation should be encouraged to effectively solve the problem of insufficient islet source.At the same time, through continuous research and development of new materials and technologies, optimize the location of islet transplantation to improve the implantation and survival of islet grafts, and gradually eliminate the need for immunosuppression.In addition, we should actively promote the development and application of post-islet transplantation graft monitoring tools to further ensure the long-term survival of post-islet transplantation grafts, so that more diabetic patients can benefit from it.

Recent advances in preclinical research of renal xenotransplantation and selection of potential recipients in the future / 中华器官移植杂志

After continuous efforts from generations of transplant surgeons, kidney transplantation (KT) has become an optimal treatment for end-stage renal disease.However, an imbalance between supply and demand of organs has always restricted the development of KT.For this clinical dilemma, xenotransplantation is expected to become one practical alternative for alleviating organ shortage.This review summarized recent literature reports of kidney xenotransplantation and the latest cases of pig-to-human kidney and heart transplantations.Also clinical transformations and applications of kidney xenotransplantation were discussed.

Transmission of porcine endogenous retrovirus in xenotransplantation / 器官移植

Organ transplantation is the most effective treatment for various types of end-stage diseases. To resolve the problem of donor shortage in organ transplantation, the possibility of xenotransplantation has been gradually explored by surgeons. Pig is one of the common donor sources for xenotransplantation. As a bridge between two species, the viruses carried by pig organs may be transmitted between species and cause the risk of zoonosis. Porcine endogenous retrovirus (PERV) is integrated into the genome, which is a category of retrovirus featuring cross-species transmission. In this article, the influencing factors of transmission characteristics of PERV, the transmission risk of PERV and its recombinant virus, and the detection and transmission risk assessment of PERV in xenotransplantation test were reviewed, aiming to provide reference for alleviating severe shortage of donor organs and driving the advancement of xenotransplantation technologies.

Attitudes and influencing factors of transplantation-related populations towards kidney xenotransplantation / 器官移植

Objective To investigate the attitudes and influencing factors of transplantation-related populations towards kidney xenotransplantation. Methods From June 2022 to January 2023, stratified random sampling was performed from patients awaiting kidney transplantation, patients after kidney transplantation, patients' relatives and medical students. Four hundred subjects were collected from each population and 1600 subjects were investigated using a self-designed questionnaire. Baseline data of the respondents, their attitudes towards kidney xenotransplantation and the reasons of rejecting kidney xenotransplantation were analyzed. The influencing factors of attitudes towards kidney xenotransplantation were also identified. Results A total of 1 493 valid questionnaires were collected, and the questionnaire retrieval rate was 93.31%. About 93.10% of the respondents accepted allogeneic kidney transplantation, and 66.78% had heard of kidney xenotransplantation. Seven hundred and ninety-five respondents suggested that they could accept kidney xenotransplantation "when kidney xenotransplantation and allogeneic kidney transplantation yielded the same results and risks". Six hundred and ninety-eight respondents indicated that they were "unable" or "uncertain" whether they could accept kidney xenotransplantation (χ2=16.409，P=0.001). Among these 698 respondents, the proportion of them who were willing to accept kidney xenotransplantation when they did not meet the conditions of allogeneic kidney transplantation was 10.9%. About 35.8% of respondents were willing to accept kidney xenotransplantation if it yielded less risk and better prognosis compared with allogeneic kidney transplantation. If the time of awaiting kidney xenotransplantation was shorter than that of allogeneic kidney transplantation, 21.2% were willing to accept kidney xenotransplantation. If the cost of kidney xenotransplantation was less than that of allogeneic kidney transplantation, 24.5% of them were willing to accept kidney xenotransplantation. The main reasons of rejecting kidney xenotransplantation included surgical risk and other unknown risks. Multivariate analysis showed that respondents residing in cities and towns for a long period of time, those who accept allogeneic kidney transplantation and those who have heard of kidney xenotransplantation showed more positive attitudes towards kidney xenotransplantation. Conclusions Different transplantation-related populations have different attitudes towards kidney xenotransplantation, and the overall attitudes are positive. Active promotion of kidney xenotransplantation research and carrying out relevant popular science education contribute to improving public attitudes towards the acceptance of kidney xenotransplantation.

Latest research progress on expansion of the donor pool for heart transplantation / 器官移植

With gradual maturity of surgical technique of heart transplantation, extensive use of immunosuppressants and the improvement of organ distribution system, the shortage of donor heart has become a bottleneck issue restricting the development of heart transplantation in clinical practice. How to expand the donor pool for heart transplantation remains to be urgently solved. In recent years, with the development of science and technology and the application of new technology, groundbreaking progresses have been made on how to expand the donor pool for heart transplantation within the transplantation community. Multiple research results have been gradually translated into clinical practice, driving the development of heart transplantation in clinical settings. In this article, the latest technologies and strategies to expand the donor pool for heart transplantation were reviewed, the roles of organ preservation technology, use of marginal donor heart, xenotransplantation, artificial heart and bioartificial heart in alleviating the shortage of donor heart were investigated, and existing challenges and future directions to expand the donor pool for heart transplantation were summarized, aiming to provide reference for subsequent development of heart transplantation in clinical practice.

Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation / 器官移植

Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K+ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β2-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.

Preliminary study of the role of IL-18/IL-18BP in mediating cytotoxic ability of NK-92MI cells against endothelial cells from GTKO porcine models / 器官移植

Objective To evaluate the role and potential mechanism of interleukin (IL)-18/IL-18 binding protein (BP) in mediating the killing effect of natural killer (NK)-92MI cells upon endothelial cells from α-1, 3- galactosyltransferase gene-knockout (GTKO) porcine models. Methods NK-92MI cells were divided into the NK, NK+IL-18, NK+GTKO, IL-18+NK+GTKO and IL-18+IL-18BP+NK+GTKO groups. The messenger ribonucleic acid (mRNA) levels of inflammation-related genes in NK-92MI cells were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The killing effect of NK-92MI cells on endothelial cells from GTKO porcine models was evaluated by lactate dehydrogenase (LDH) assay. The apoptosis of endothelial cells from GTKO porcine models was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The expression levels of proteins with killing effect and apoptosis-related proteins were determined by Western blot. Results Compared with the NK, NK+IL-18 and NK+GTKO groups, the expression levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-8, IL-3, IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA were up-regulated in NK-92MI cells in the IL-18+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the IL-18+NK+GTKO group, the expression levels of IFN-γ, TNF-α, IL-8, IL-3, IL-6 and GM-CSF mRNA were down-regulated in NK-92MI cells in the IL-18+IL-18BP+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the NK+GTKO group, the expression levels of perforin, granzyme B and IFN-γ proteins in NK-92MI cells were up-regulated, the killing rate of NK-92MI cells against endothelial cells from GTKO porcine models was enhanced, the apoptosis rate of endothelial cells from GTKO porcine models was increased, and the ratios of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/Bcl-2 and cleaved Caspase-3/Caspase-3 in endothelial cells from GTKO porcine models were elevated in the IL-18+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the IL-18+NK+GTKO group, the expression levels of perforin, granzyme B and IFN-γ proteins were down-regulated, the killing rate of NK-92MI cells against endothelial cells from GTKO porcine models was decreased, the apoptosis rate of endothelial cells from GTKO porcine models was decreased, and the ratios of Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 in endothelial cells from GTKO porcine models were declined in the IL-18+IL-18BP+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Conclusions IL-18BP may block the expression of inflammation-related genes in NK-92MI cells induced by IL-18 and the killing effect of NK-92MI cells on endothelial cells from GTKO porcine models.

The past, present and future of heart transplantation / 器官移植

Heart transplantation is one of the most effective strategies to treat end-stage heart failure. Multiple challenges, such as difficulty in preservation of heart allograft, rejection and postoperative complications, emerge in heart allotransplantation. After decades of research and practice, most problems have been resolved. Nevertheless, the shortage of donor organs has become increasingly prominent. To alleviate the shortage of donor organs, artificial heart and heart xenotransplantation have captivated attention, and obtained significant progress in recent years. The application of artificial heart in clinical practice has significantly enhanced the survival rate of patients with end-stage heart failure, which is expected to become the standard treatment for end-stage heart failure. Heart xenotransplantation still faces many challenges, which is still far from clinical application. In this article, the history of heart transplantation, development of heart allotransplantation, use of artificial heart and research progress on heart xenotransplantation were reviewed, and the future development direction of heart transplantation was predicted.

Are we ready for pig-to-human clinical xenotransplantation trials? / Estamos prontos para ensaios clínicos de xenotransplante porco-para-humanos? / ¿Estamos listos para ensayos clínicos de xenotrasplante del cerdo al humano?

Abstract: The invention and widely use of organ allotransplantation provides effective treatment of some originally fetal diseases such as liver/kidney failure and has saved million of lives around the globe. However, the scarcity of human organs has caused many patients, who could have been treated, to die while waiting for suitable organs around the world. Pig-to human xenotransplantation provides a potential solution to solve this tough problem. Pig organs have been considered as major sources of xenotransplantation because of the sufficient number of donors, the sizes of organs, and physiologically structural similarities. However, xenotransplantation also has some problems, such as the possibility of spreading animal diseases to human, the interspecies immunological barrier, organs of animal origin challenging human nature, and potential informed consent issues. This article will discuss these potential issues and to see whether it is the suitable time to conduct clinical xenotransplantation trials in humans.

Resumen: La invención y el amplio uso de trasplantes alógenos proporciona tratamiento efectivo de algunas enfermedades de origen fetal, como la insuficiencia renal y hepática, y ha salvado a millones de pacientes en el mundo. Sin embargo, la escasez de órganos humanos ha causado que muchos pacientes en el mundo, que podrían haber sido tratados, murieran por esperar un órgano adecuado. El xenotrasplante del cerdo al humano proporciona una solución potencial para resolver este difícil problema. Los órganos de cerdo han sido considerados como fuentes mayores para xenotrasplantes debido al suficiente número de donantes, el tamaño de los órganos y estructuras fisiológicas similares. No obstante, el xenotrasplante también tiene algunos problemas, como la posibilidad de expandir enfermedades animales a humanos, la barrera inmunológica entre especies, el desafío para la naturaleza humana de tener órganos de origen animal y problemas potenciales de consentimiento informado. Este artículo discute estos temas potenciales y plantea si estamos en un momento apropiado para realizar ensayos clínicos de xenotrasplantes en humanos.

Resumo: A invenção e amplo uso de alotransplante de órgãos propicia tratamento efetivo para algumas doenças originalmente fetais tais como falência hepática/renal e tem salvo milhões de vidas em todo o globo. Entretanto, a escassez de órgãos humanos tem causado a morte de muitos pacientes que poderiam ter sido tratados - aguardando por órgãos apropriados em todo o globo. Xenotransplante porco-para-humanos propicia uma solução potencial para resolver este difícil problema. Órgãos de porco tem sido considerados como as principais fontes de xenotransplante por causa do número suficiente de doadores, do tamanho dos órgãos e de similaridades estruturais fisiológicas. Entretanto, xenotransplante também tem alguns problemas, tais como a possibilidade de disseminar doenças animais aos humanos, a barreira imunológica entre espécies, órgão de origem animal desafiando a natureza humana e aspectos potenciais de consentimento informado. Esse artigo discutirá esses aspectos potenciais e verificará se é o momento adequado para conduzir ensaios clínicos de xenotransplante em humanos.

Current status and prospect of surgical technique of liver transplantation / 器官移植

Along with the increasing quantity of patients with end-stage liver diseases year by year, as an efficacious treatment, the safety and efficacy of liver transplantation are critical issues to be considered. In addition, liver transplant techniques have become a new research hot spot. In recent years, liver transplant techniques are constantly innovating and developing with the unremitting efforts of researchers. Researchers have successively developed multiple liver transplant techniques, such as split liver transplantation, ischemia-free liver transplantation, liver xenotransplantation, domino liver transplantation, delayed total hepatectomy combined with liver resection and segment Ⅱ-Ⅲ liver transplantation, heterotopic auxiliary liver transplantation on splenic fossa and magnetic anastomosis. It has laid a foundation for expanding the donor pool, improving clinical efficacy of liver transplantation and enhancing the quality of life of liver transplant recipients. In this article, the exploration, development, innovation and improvement of liver transplant techniques were reviewed and prospected, aiming to provide reference for clinical application of liver transplantation.