In recent years, breakthroughs in genetic engineering (GE) and cloning technology have led to the successful cultivation of “designated pathogen free (DPF) xenotransplantation (XENO) medical (M) pigs” (hereinafter referred to as GE-DPF-XENO-M pigs). Based on GE-DPF-XENO-M pigs, a large number of xenotransplantation experiments with non-human primates (NHPs) as recipients basically answered the most concerned questions: overcoming hyperacute rejection and cross species infection. These achievements directly accelerate to the emergence of a new “xenotransplantation subclinical research model”. At the end of 2021, Montgomery and Porrett teams in the United States successively transplanted GE pig kidney into the remains of 3 brain dead cases, no hyperacute rejection occurred after 48–72 hours. These three subclinical studies provide a scientific basis for xenotransplantation into clinical research. On January 7, 2022, Griffith, Maryland, USA, etc. transplanted a GE pig heart to a patient with severe heart failure and survived for 59 days. The above progress shows that xenotransplantation has taken a key step towards the stage of clinical research, which is worthy of our peers’ attention and reference.
Objective To review the research progress of Toll-like receptors (TLRs) signaling and its effects in organ transplantation. Methods The structural and functional features of TLRs and their ligands were summarized,the literatures in recent years about the research progress of TLRs signaling in animal experiment and clinical organ transplantation were reviewed. Results TRLs played an important role in the organ transplantation,the activation of TLRs could activate the specific immune system,and contribute to ischemic reperfusion injury,acute and chronic allograft rejections,and induce the immune tolerance. Early treatment intervention could reduce the activation of TRLs through ischemic reperfusion injury in the organ transplantation,and improve the allograft survival. The efficient immunosuppressive drugs which aimed at the related immunosuppressive target in immune and its signal transduction pathway could reduce ischemic reperfusion injury in the organ transplantation and immune rejection. Conclusions TRLs signaling plays an important role in ischemic reperfusion injury,immune rejection,and immune regulation.
ObjectiveTo compare tacrolumus (FK506) with cyclosporine A (CsA) in clinical application to organ transplantation.MethodsThe literature in recent years has been reviewed and compared. ResultsFK506 was a powerful immunosuppression with a mechanism of action similar to that of CsA, but significantly superiori to CsA in terms of prophylaxis and treatment of allograft acute rejection, delay of chronic rejection, and withdrawal of steroid in early period. The cardiovascular mortality and chronic graft nephropathy (CGN),such as hypertension and hyperlipidemia were less frequently seen in FK506treated patients and FK506 also had an acceptable safety profile, including a low incidence of hypertrichosis,gingival hyperplasia and infections.However, CsA had been showed a better result in prevention of posttransplantation diabetes mellitus (PTDM ) and more economic agent than FK506. Pharmacokinetic studies showed CsA in the form of Sandimmun Neoral showed less inter an intrapatient variability than FK506.Meanwhile, the combination of MMF and FK506 or CsA has been proved effectively with excellent graft and patients survival. Conclusion FK506 and CsA are safe and effective long term maintenance immunosuppressive agents in organ transplantation with wonderful prospect.
ObjectiveTo summarize the research progress of surgical technique and immunosuppressive regimen of abdominal wall vascularized composite allograft transplantation in animals and clinical practice. MethodsThe literature on abdominal wall transplantation at home and abroad in recent years was extensively reviewed and analyzed. ResultsThis review includes animal and clinical studies. In animal studies, partial or total full-thickness abdominal wall transplantation models have been successfully established by researchers. Also, the use of thoracolumbar nerves has been described as an important method for functional reconstruction and prevention of long-term muscle atrophy in allogeneic abdominal wall transplantation. In clinical studies, researchers have utilized four revascularization techniques to perform abdominal wall transplantation, which has a high survival rate and a low incidence of complications. ConclusionAbdominal wall allotransplantation is a critical reconstructive option for the difficulty closure of complex abdominal wall defects. Realizing the recanalization of the nerve in transplanted abdominal wall to the recipient is very important for the functional recovery of the allograft. The developments of similar research are beneficial for the progress of abdominal wall allotransplantation.
Objective To investigate the immunoregulatory effects of immunonutrient ω-3 polyunsaturated fatty acid (PUFA) and its applications in organ transplantation. Methods Relevant literatures of recent years were reviewed. Results The immunoregulatory effects of ω-3 PUFA can inhibit proliferation and activation of the immunocompetent cells including T cell and B cell, reduce cytokine production, modulate immunologic response, improve graft function, pro-long survival, reduce episodes of rejection, and lessen adverse reactions of immunosuppressor.Conclusion ω-3 PUFA should have wide applications in organ transplantation due to its immunoregulatory effects. However, this research should be further studied.
Objective To investigate the impact of immunonutrition in organ transplantation.Methods The literatures of recent years on the studies of immunonutrition in organ transplantation were reviewed. Results Immunonutrition including ω-3 fatty acid and special amino acids etc could reduce inflamation and supress immunal response following organ transplantation markably. Conclusion Application of immunonutrition associated with immunosupress could take the place of traditional steroids completely in the treatment following organ transplantation, even shorten clinical course of immunosupress.
Objective To summarize the application and progress of common autologous organ transplantation (AOT) techniques. Method A literature review and summary of previous and recent studies on common AOT was performed, including autologous liver transplantation, autologous kidney transplantation and intestinal autotransplantation techniques. Results AOT solved the issues of bleeding that cannot be controlled by in vivo resection of lesions, difficulties in vascular reconstruction, and the inability to radically resect lesions, and extended the indications for treatment of partially diseased conditions. Conclusions The AOT technique has an ameliorating effect on the tight donor situation in China, providing more potential donors. And the application of the AOT technique effectively avoids the usage of postoperative immunosuppressive drugs and the progression of lesions due to waiting for allogeneic organ transplantation. However, the clinical benefit in malignant tumors remains to be further investigated.
ObjectiveTo systematically review the efficacy and safety of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKA) in solid organ transplant (SOT) recipients. MethodsThe PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang Data, CBM and VIP databases were electronically searched to collect clinical studies on DOACs (rivaroxaban, apixaban, idoxaban, dabigatran) compared with VKA in SOT recipients from inception to May 15, 2024. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software. ResultsA total of 11 cohort studies involving 1 408 SOT recipients were included. The meta-analysis results showed that compared with VKA, DOACs could reduce the risk of any bleeding (RR=0.47, 95%CI 0.37 to 0.60, P<0.05) and major bleeding (RR=0.56, 95%CI 0.37 to 0.84, P<0.05) in SOT recipients. But there were no statistically significant differences in the total incidence of thrombotic events, VTE incidence, and stroke incidence between the two groups. ConclusionCurrent evidence shows that DOACs are not inferior to VKA in anticoagulation therapy for SOT recipients, but they perform better in terms of any bleeding and major bleeding. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.