p53基因转移至移植心脏的安全性

背景：课题组前期实验表明野生型p53基因具有抑制移植心脏冠状动脉内膜增厚的作用。 目的：研究腺病毒介导的野生型p53基因转移至移植心脏的安全性。 方法：以Wistar大鼠为供体,SD大鼠为受体建立大鼠腹腔异位心脏移植模型,在取出供心后,经供心冠状动脉分别注射携带野生型p53基因的重组腺病毒液、携带β-半乳糖酐酶基因的重组腺病毒液和生理盐水800 µL,4 ℃静置30 min后进行心脏移植。 结果与结论：移植后 5 d,重组腺病毒液组的供心冠状动脉组织可见野生型P53蛋白的表达。移植后28 d,未见受体大鼠血液生化学指标异常和重要脏器的病理性改变,RT-PCR扩增未见腺病毒E1A区产物。说明在心脏移植中,将腺病毒介导的野生型p53基因转移至移植心脏是安全的。     

Non heart-beating donors in England

When transplantation started all organs were retrieved from patients immediately after cardio-respiratory arrest, i.e. from non heart-beating donors. After the recognition that death resulted from irreversible damage to the brainstem, organ retrieval rapidly switched to patients certified dead after brainstem testing. These heart-beating-donors have become the principal source of organs for transplantation for the last 30 years. The number of heart-beating-donors are declining and this is likely to continue, therefore cadaveric organs from non-heart-beating donor offers a large potential of resources for organ transplantation. The aim of this study is to examine clinical outcomes of non-heart-beating donors in the past 10 years in the UK as an way of decreasing pressure in the huge waiting list for organs transplantation.     

肝癌肝切除后的复发补救性肝移植治疗

背景：在当前供肝紧缺的情况下,补救性肝移植策略的提出为缓解这个问题提供了新的方向。 目的：对比符合Milan标准肝癌患者肝切除后复发再行补救性肝移植和直接行肝移植的疗效。 方法：选择2001-07/2009-08在解放军南京军区福州总院肝胆外科接受肝移植治疗,符合Milan标准的肝癌患者53例,其中12例符合Milan标准肝切除后复发再行肝移植,作为补救性肝移植组,41例行直接肝移植。 结果与结论：补救性肝移植组手术时间、无肝期、术中出血量、术中悬浮红细胞输注量、ICU时间、住院总时间、住院总费用明显高于直接肝移植组(P > 0.05),两组术中冰冻血浆输注量比较差异无显著性意义(P < 0.05)。随访39个月,两组总体生存率差异无显著性意义(P > 0.05)。说明对于符合Milan标准的肝癌患者首次行肝切除,待其复发再行肝移植也是一种可行的策略。     

Recent advances in understanding xenotransplantation: implications for the clinic

The results of organ and cell allotransplantation continue to improve, but the field remains limited by a lack of deceased donor organs. Xenotransplantation, for example, between pig and human, offers unlimited organs and cells for clinical transplantation. The immune barriers include a strong innate immune response in addition to the adaptive T-cell response. The innate response has largely been overcome by the transplantation of organs from pigs with genetic modifications that protect their tissues from this response. T-cell-mediated rejection can be controlled by immunosuppressive agents that inhibit costimulation. Coagulation dysfunction between the pig and primate remains problematic but is being overcome by the transplantation of organs from pigs that express human coagulation-regulatory proteins. The remaining barriers will be resolved by the introduction of novel genetically-engineered pigs. Limited clinical trials of pig islet and corneal transplantation are already underway.     

ABO-incompatible organ transplantation

Increases in the patients on the organ transplant wait list have far out paced the number of available organs. This has lead to longer time awaiting transplantation and thus increased morbidity and mortality associated with it. Making more organs available for transplantation remains critical, and hence, extended criteria donors and ABO-incompatible organs are being utilized. Recent reports on the use of conventional immunosuppressive regimens for ABO-incompatible grafts suggest outcomes can be obtained similar to those of ABO-compatible transplants. The delay in the development of natural antibodies to ABO antigens in infants provides an 'immunological window' that allows for successful ABO-incompatible transplants in this age group. This also allows for a unique mechanism long-term tolerance to the graft in infants. ABO incompatibility may no longer be a contraindication in case of kidney transplantation and paediatric heart transplantation. Increased utilization of ABO-incompatible grafts can alleviate the shortage for organs and decrease waitlist times and associated morbidity. In this review, we will discuss the current status of ABO-incompatible transplantation in adult and paediatric solid organ transplantation with attention on recent developments on understanding the mechanisms of graft acceptance in these ABO-incompatible organs.     

Ethicolegal issues of organ donation as the main obstacle to the progress of clinical transplantation

Ethicolegal issues present the main factor hindering obtaining organs from corpses and living donors, the distribution of cadaveric organs, and the financial providence of donorship in Russia. The actual Russian legislation is contradictory in terms of obtaining relatives' consent for the transplantation of cadaveric organs. There are no precise definitions of the degree of genetic relationship between the donor and recipient sufficient for transplantation. Selling and purchasing human organs is strictly prohibited, while financial compensation of the living donor seems to be a fair measure. Providing the possibility to verify brain death is a necessary condition for expanding the cadaveric organ pool. The organ shortage leads to improper distribution of donor organs. All these problems have to be solved for the progress of organ transplantation in Russia.     

Discordant xenografting: challenges and controversies.

The transplantation of organs between individuals of disparate species is being considered as a potential solution to a serious shortage of donor organs for clinical transplantation. We summarize recent papers concerning the immunologic barrier to xenotransplantation, the pathogenesis of hyperacute rejection and reports on efforts made to prevent or mitigate hyperacute xenograft rejection.     

EPR spectroscopy as a predictive tool for the assessment of marginal donor livers perfused on a normothermic ex vivo perfusion circuit

Liver transplantation is a highly successful treatment for end-stage liver disease. While liver transplantation is often the only effective treatment for cirrhosis there is a critical shortage of donor organs, leading to death of many potential recipients on the waiting list. Marginal liver grafts are increasingly being used in an attempt to increase the number of donor livers utilized for transplantation. Marginal donor livers often have complications and worse outcomes for recipients receiving these types of transplant. The ability to predict the outcome with the use of marginal grafts is difficult and often imprecise leading decreased use of potentially suitable grafts. The development and maturation of normothermic ex vivo perfusion as a platform for the assessment of donor organs presents an opportunity to increase the number of usable donor livers available for transplantation. Furthermore, direct measurement of reactive oxygen species (ROS) present in the donor liver on an ex vivo perfusion circuit by electron paramagnetic resonance (EPR) spectroscopy would allow for precise real-time quantification of donor organ injury. The combination normothermic ex vivo liver perfusion with EPR spectroscopy could therefore present a powerful platform to increase the number of donor organs utilized for transplantation.     

肝肾胰器官簇移植临床解剖学研究

目的：为了开展肝肾胰器官簇移植提供应用解剖学资料和术式设计方案。方法：对２４具成人尸体进行解剖观察,了解其主要血管分布,胆管、输尿管、胰管的位置以及腹腔内空腔脏器的相互关系。结果：测得主要血管腹主动脉平均长度１９．２０ｃｍ,上端外径２．２１ｃｍ;下腔静脉平均长度１９．４２ｃｍ,上端外径２．６０ｃｍ;门静脉长５．５９ｃｍ,宽度１．４９ｃｍ;肝固有动脉长３．８５ｃｍ,宽０．６４ｃｍ;胆总管长４．１９ｃｍ,宽度０．７８ｃｍ;在输尿管平均长度为２７．１１ｃｍ,右输尿管平均长度为２５．９３ｃｍ。对器管簇移植的整体切取、修整、安放和吻合提供多种方案。结论：肝肾胰器官簇移植手术有应用解剖学依据的可行性,按形态学规律有多种合理的术式设计方案     

Kidney Transplantation From Deceased Donors With Bloodstream Infection: A Multicenter Retrospective Study

BackgroundThe use of organs from donors with infection is limited because of the possibility of transmission. We aimed to investigate the transmission after deceased donor transplantation with bloodstream infection (BSI).MethodsA retrospective study of patients undergoing kidney or pancreas transplantation at five tertiary centers in Korea from January 2009 and November 2019 was performed. We analyzed the outcomes after transplantation from deceased donors with BSI.ResultsEighty-six recipients received transplantation from 69 donors with BSI. The most common isolated pathogens from donors were Gram-positive bacteria (72.0%), followed by Gram-negative bacteria (22.7%), and fungi (5.3%). Appropriate antimicrobial agents were used in 47.8% of donors before transplantation. Transmission occurred only in 1 of 83 recipients (1.2%) from bacteremic donors and 1 of 6 recipients (16.7%) from fungemic donors. One-year patient and graft survival was 97.5%and 96.3%, respectively. There was no significant difference in graft and patient survival between patients who received organs from infected donors and noninfected donors.ConclusionUsing organs from donors with bacteremia seems to be a safe option with low transmission risk. The overall prognosis of using organs from donors with BSI is favorable.     

Development of Natural Killer Cells: Comparison of the Maturation Rates in Different Lymphoid Compartments

By means of semisyngeneic bone marrow transplantation, the appearance of donor-type natural killer (NK) cells in different organs (spleen, blood, lungs) of the recipients was studied. Seven days after the transplantation the first donor-type NK cells appeared in all these organs, and adult NK levels were reached simultaneously within a couple of days. The first NK cells to appear in every organ divided rapidly (sensitive to hydroxyurea) and contained a high proportion of Thy-1+ cells. These data suggest that NK cell precursors mature locally and simultaneously in different organs.     

大鼠原位与异位肾移植三维数字化构建方法的初步研究

目的　探讨使用3ds Max软件的空间建模技术实现对大鼠原位与异位肾移植仿真模拟的简单方法。 方法　根据大鼠实体解剖，使用Autodesk 3ds Max 8 SP2软件运用放样、布尔运算、多边形造模、倒角剖面和车削等手段，对肾、肾上腺、血管、膀胱、气管、甲状腺和血管等器官进行真实比例构建，合并到腹部及颈部移植场景中，并安装自由摄像头经渲染后获取各角度的三维图像。 结果　成功构建出肾移植相关器官以及大鼠原位，右髂窝位及颈前部的肾移植场景，可作为动物实验的可靠参考，提高手术成功率。 结论　3ds Max的三维非几何体形状器官的造模及场景构建方法，具有可重复性强，方法简单，在个人电脑上易实现的特点。     

Potential of Anticomplement Therapy in Clinical Transplantation

The activation of complement contributes to tissue damage in many ways. Prevention of complement activation in organ transplantation has largely centred on studies in xenotransplantation, where complement plays a key role in the pathogenesis of hyperacute rejection. Transgenic porcine organs expressing human regulators of complement activation in combination with soluble inhibitors as well as appropriate immunosuppression may be sufficient to alleviate the major immunological barriers that currently prevent the use of xenogeneic organs for human transplantation.     

Transplantation and the trauma surgeon

The number of satisfactory vascular organs suitable for organ transplantation can be increased appreciably by a close working relationship between traumatologists and transplant surgeons. Benefits will derive from more precise and rapid field management of brain-injured patients, with subsequent appropriate stabilization. If brain death is declared, prompt referral for organ donation with optimal management should result in well-functioning organs for transplantation. A defined team approach with well-defined protocols could solve most of the medical and moral dilemmas. Compassionate emotional support should be provided for families, particularly minorities, and should extend to inexperienced staff. Underlying these goals are a strong institutional commitment to staff education and an understanding of the lifesaving role that organ transplantation can play.     

Artificial organs and transplantation

Nowadays artificial devices are not able to totally and undefinitely replace the loss of function of all vital organs and artificial organs can be used only to bridge the time to transplantation, which must be considered the first choice in the therapeutical approach for many chronic diseases. Since general population aging process is leading to an increase of organ demand, the gap between performed and requested transplantation is hard to fill. Xenotransplantation is nowadays only an experimental alternative solution and we have to do our best using available artificial organs to increase and improve the survival of patients waiting for transplantation. In this meeting we particularly dealt about organ function replacing therapy, especially regarding the kidney, heart, liver, pancreas and ear.     

Transmission of hepatitis C virus by organ transplantation.

BACKGROUND. Liver disease is a frequent and major complication after organ transplantation. We sought to determine whether hepatitis C virus (HCV) is transmitted by organ transplantation and whether it causes post-transplantation liver disease. METHODS. Serum samples from all cadaver organ donors to the New England Organ Bank between 1986 and 1990 were screened retrospectively for antibodies to HCV (anti-HCV) by enzyme-linked immunosorbent assay (ELISA). We reviewed the hospital records of all recipients of organs from anti-HCV-positive donors for evidence of liver disease. Serum samples from recipients obtained before transplantation and during follow-up were analyzed for anti-HCV. RESULTS. Of 716 organ donors, 13 (1.8 percent) were positive for anti-HCV. Their organs (19 kidneys, 6 hearts, and 4 livers) went to 29 recipients. Non-A, non-B hepatitis developed after transplantation in 14 of the 29 (48 percent), for a prevalence 7.4 times the 6.5 percent prevalence after transplantation from untested donors that was previously reported by two institutions in the organ bank (P less than 0.0001). The liver disease began a mean of 3.8 months after transplantation and became chronic in 12 patients; the other 2 had subfulminant hepatic failure. Liver disease was more frequent in the patients who had received antilymphocyte preparations (P = 0.04). HCV was the cause of the post-transplantation liver disease in 12 of the 13 recipients (92 percent) for whom serum samples were available. Anti-HCV was detected by ELISA in eight and enzyme immunoassay in one; in three others, HCV RNA was detected by polymerase chain reaction in serum samples obtained after transplantation. CONCLUSIONS. Organ transplantation can transmit hepatitis C. This raises serious questions about the continued acceptance of organs from donors positive for anti-HCV.     

CD47: a new player in phagocytosis and xenograft rejection

Organ transplantation is limited by the availability of human donor organs. The transplantation of organs and tissues from other species (xenotransplantation) would supply an unlimited number of organs and offer many other advantages for which the pig has been identified as the most suitable source. However, the robust immune responses to xenografts remain a major obstacle to clinical application of xenotransplantation. The more vigorous xenograft rejection relative to allograft rejection is largely accounted for by the extensive genetic disparities between the donor and recipient. Xenografts activate host immunity not only by expressing immunogenic xenoantigens that provide the targets for immune recognition and rejection, but also by lacking ligands for the host immune inhibitory receptors. This review is focused on recent findings regarding the role of CD47, a ligand of an immune inhibitory receptor, signal regulatory protein alpha (SIRPα), in phagocytosis and xenograft rejection.     

Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation

On line of thought in organ transplantation feels that immunosuppressive drugs can lead to tolerance induction by allowing a previously unrecognized common mechanism of cell migration and microchimerism to occur perist, and in some cases, become drug independent. It has been recognized that there is a spectrum of susceptibility of different organs to cellular rejection and that the variable ability of these organs to induce donor-specific nonreactivity reflects their comparative content of migratory leukocytes. Here, Thomas Starzl and colleagues discuss how many of the enigmas of transplantation immunology can be explained by this chimerism.     

Transplantation of embryonic hepatocytes. Experimental substantiation of a new approach to the therapy of liver failure

The use of embryonic cells for the therapy of insufficiency in vitally important organs is a promising approach of transplantation medicine. Transplantation of fetal cells can restore liver functions during severe failure of various geneses. We review modern notions about histogenesis, structure, and mechanisms of functioning of low differentiated hepatocytes and extrahepatic cells that can be used for transplantation. Methods for ex vivo isolation of fetal cells for transplantation are described.