自1989年巴西医生Raia开展人类首例活体肝移植(living donor liver transplantation, LDLT)以来,LDLT受体的优良预后及供体的安全性逐步得到了公认,加之“脑死亡”供肝的严重匮乏,LDLT技术迅速发展并被公认为是缓解供肝来源匮乏最有效的方法之一[1,2]。LDLT技术的发展大致经历了三个阶段: ①成人→儿童间活体肝移植(简称儿童活体肝移植,pediatric living donor liver transplantation, PLDLT); ②成人→成人间活体肝移植(adulttoadult living donor liver transplantation, ALDLT); ③急诊活体肝移植(emergency or highurgency living donor liver transplantation, ELDLT )。LDLT技术发展的每一阶段均是对前一阶段技术的总结和升华,技术难度和复杂性也逐步增加。
Abstract: Cardiac transplantation is an effective therapeutic method for terminalstage heart diseases. The immunosuppressive treatment based on calcineurin inhibitors (CsA and FK506) is most commonly used, monoclonal antibodies are also used in some recipients as induction therapy before and/or after transplantation. Some new immunosuppressive drugs, such as Rapamycin and Everolimus, can not only inhibit the acute transplant rejection but also prevent cardiac vasculopathy. The application of some relatively nontraumatic tests, such as immunological indexes, cardiac markers and other serological parameters, are helpful for diagnosis and preventing postcardiac transplant rejection at early stage and improving the result of cardiac transplantation.
Objective To study the effect of recombinant lentiviral vector mediated human hepatocyte growth factor (hHGF) gene-modified bone marrow mesenchymal stem cells (BMSCs) on the immunological rejection after allograft l iver transplantation in rats, and to reveal the mechanism of immune tolerance. Methods Eight male Sprague Dawley (SD)rats of clean grade (aged 3 to 4 weeks, weighing 75-85 g) were selected for the isolation and culture of BMSCs; 64 adult male SD rats of clean grade (weighing 200-250 g) were used as donors; and 64 adult male Wistar rats of clean grade (weighing 230-280 g) were used as receptors. After establ ishing a stable model of rat allogeneic l iver transplantation, 1 mL sal ine, 2 ×106/mL of BMSCs 1 mL, 2 × 106/mL of BMSCs/green fluorescent protein 1 mL, and 2 × 106/mL of BMSCs/hHGF 1 mL were injected via the portal vein in groups A, B, C, and D respectively. Then the survival time of the rats was observed. The hepatic function was determined and the histological observation of the l iver was performed. The hHGF mRNA expression was detected by RT-PCR, the level of cytokine including hHGF, interleukin 2 (IL-2), IL-4, IL-10, and interferon γ (IFN-γ) by ELISA assay, the level of apoptosis by TUNEL method, and the expression level of prol iferating cell nuclear antigen (PCNA) by immunohistochemical method. Results The survival time of group D was significantly higher than that of groups A, B, and C (P lt; 0.01); the survival time of groups B and C was significantly higher than that of group A (P lt; 0.01), but there was no significant difference between group B and group C (P gt; 0.05). RT-PCR demonstrated the transcription of hHGF mRNA in the grafts of group D; the serum cytokine hHGF reached to (6.2 ± 1.0) ng/mL. Compared with groups B and C, group D exhibited significant inhibitory effect, significantly improved l iver function, and showed mild acute rejection. In addition, the levels of cytokine IL-2 and IFN-γ decreased; the levels of cytokine IL-4 and IL-10 increased; the level of apoptosis reduced; and the expression level of PCNA increased. Except for the expression of IL-4 (P gt; 0.05), there were significant differences in the other indexes between group D and groups B, C (P lt; 0.05). Conclusion BMSCs/hHGF implanting to rat l iver allograft via portal vein can induce immune tolerance. Compared with injection of BMSCs alone, BMSCs/hHGF treatment can alleviate acute rejection and prolong the survival time significantly. The immunosuppressive effect of BMSCs/hHGF is correlated with Th2 shifts up of Th1/Th2 shift, reduced apoptosis, promoted l iver regeneration.
Objective To review the research progress of composite tissue allotransplantation (CTA), analyzethe superiority and the inferiority, and inform the possible direction of further research. Methods Literature concerningCTA was reviewed and analyzed in terms of the l imits of conventional reparative and reconstructive surgery, the definitionof CTA, potential advantages, and treatment risks. Results The cl inical research of CTA both at home and abroad proved that the therapeutic effect of CTA was better than that of conventional reparative and reconstructive surgery. However, therisks resulting from immunosuppressive therapy were still the primary factors restraining the wide cl inical appl ication ofCTA. Conclusion The development of immunosuppressive therapy explores a great development potential for the CTA, and how to decrease the treatment risk of immunosuppressive therapy will be the main research direction in the field of CTA.