Classic Transplantation Research Articles

A Case Report of Modified Pancreatic Transplantation With a Limited Splenic Arteriovenous Fistula to Elude Thrombosis

In classic pancreatic transplantation, the splenic artery and vein are ligated at the tail of the pancreas graft. This leads to slowed blood flow in the splenic vein and may cause thrombosis and graft loss. In this study, a patient received a pancreas after kidney transplantation. A modified surgical technique was used in the pancreatic graft preparation. The donor splenic artery and vein were anastomosed end to end at the tail of the pancreas. The splenic artery near the anastomosis was partially ligated, and an effective diameter of 2 mm was reserved to limit arterial blood pressure and flow. The patient recovered very well. Contrasted computed tomography scans on days 11 and 88 after pancreas transplantation indicated sufficient backflow of the splenic vein. We believe that this procedure may avoid the risk of splenic vein thrombosis after pancreas transplantation. This modified technique has not been reported in clinical cases previously and may help reduce the risk of thrombosis after pancreas transplantation.

Assessment of HLA-DPB1 genetic variation using an HLA-DP tool and its implications in clinical transplantation.

HLA-DP is a classic transplantation antigen that mediates alloreactivity through T-cell epitope (TCE) diversity and expression levels. A current challenge is to integrate these functional features into the prospective selection of unrelated donor candidates for transplantation. Genetically, HLA-DPB1 exon 2 defines the permissive and nonpermissive TCE groups, and exons 2 and 3 (in linkage with rs9277534) indicate low- and high-expression allotypes. In this study, we analyzed 356 272 exon 2-exon 3-phased sequences from individuals across 5 self-identified race and ethnicity categories: White, Hispanic, Asian or Pacific Islander, Black or African American, and American Indian or Alaskan Native. This sequence data set revealed the complex relationship between TCE and expression models and the importance of exon 3 sequence data. We also studied archived donor search lists for 2545 patients who underwent transplantation from an HLA-11/12 unrelated donor mismatched for a single HLA-DPB1 allele. Depending on the order in which the TCE and expression criteria were considered, some patients had different TCE- and expression-favorable donors. In addition, this data set revealed that many expression-favorable alternatives existed in the search lists. To improve the selection of candidate donors, we provide, disseminate, and automate our findings through our multifaceted tool called Expression of HLA-DP Assessment Tool, consisting of a public web application, Python package, and analysis pipeline.

Therapeutic Cell Repopulation of the Liver: From Fetal Rat Cells to Synthetic Human Tissues.

Progenitor cells isolated from the fetal liver can provide a unique cell source to generate new healthy tissue mass. Almost 20 years ago, it was demonstrated that rat fetal liver cells repopulate the normal host liver environment via a mechanism akin to cell competition. Activin A, which is produced by hepatocytes, was identified as an important player during cell competition. Because of reduced activin receptor expression, highly proliferative fetal liver stem/progenitor cells are resistant to activin A and therefore exhibit a growth advantage compared to hepatocytes. As a result, transplanted fetal liver cells are capable of repopulating normal livers. Important for cell-based therapies, hepatic stem/progenitor cells containing repopulation potential can be separated from fetal hematopoietic cells using the cell surface marker δ-like 1 (Dlk-1). In livers with advanced fibrosis, fetal epithelial stem/progenitor cells differentiate into functional hepatic cells and out-compete injured endogenous hepatocytes, which cause anti-fibrotic effects. Although fetal liver cells efficiently repopulate the liver, they will likely not be used for human cell transplantation. Thus, utilizing the underlying mechanism of repopulation and developed methods to produce similar growth-advantaged cells in vitro, e.g., human induced pluripotent stem cells (iPSCs), this approach has great potential for developing novel cell-based therapies in patients with liver disease. The present review gives a brief overview of the classic cell transplantation models and various cell sources studied as donor cell candidates. The advantages of fetal liver-derived stem/progenitor cells are discussed, as well as the mechanism of liver repopulation. Moreover, this article reviews the potential of in vitro developed synthetic human fetal livers from iPSCs and their therapeutic benefits.

The application of magnetic anchoring traction device in assisting donor liver bench surgery in classic orthotopic liver transplantation

ObjectiveTo explore the clinical application of a newly developed magnetic anchoring traction (MAT) system in the liver bench trimming and transplantation surgery.BackgroundThe conventionally limited space, vision, and exposure have always been a challenge for the quality of surgery in the liver bench trimming due to the fact that the exposure depends largely on the experience of surgeon. To deal with this problem, a MAT system is developed as an alternative support to enhance exposure. The preliminarily experiments on animals verified its feasibility and reliability in the practical use, and its clinical application and effects were examined in the present research.MethodsA total of 20 DCD (donation of cardiac death) donor livers were collected and divided evenly between the magnetic anchor traction (MAT) assisted group (n = 10) and the manual assisted group (n = 10). The results and quality assessment from experts about the liver bench surgery performed by two groups were examined and compared.ResultsThe MAT system can be employed effectively to compete and replace the manual assistance to achieve a better exposure in the liver bench trimming. No statistical difference was found regarding the baseline data between the MAT and the manual groups. In the inferior vena cava and hepatic artery trimming, the MAT group outperformed the manual group remarkably in many aspects. The surgery time for liver bench shortened considerably after a quick grasp of MAT skills by surgeons.ConclusionThe MAT system provides a more stable, reliable and qualified local exposure in the liver bench surgery, and can preferably be employed to replace the manual assistance in the procedures of liver transplantation.

The Effects of sodium bicarbonate Ringer's solution on acute kidney injury and the clinical outcomes after liver transplantation: A randomized controlled trial.

Background: Acute kidney injury is the most common complication after liver transplantation. Sodium bicarbonate Ringer’s solution is a new type of crystalloid solution that has been recently used in the clinical setting. Whether sodium bicarbonate Ringer’s solution reduces the occurrence of postoperative AKI and improves the clinical outcomes of liver transplantation patients is not clear. Objective: To compare the effects of sodium bicarbonate Ringer’s solution versus normal saline on acute kidney injury and clinical outcomes following classic orthotopic liver transplantation. Methods: Sixty-four participants were randomly assigned to the sodium bicarbonate Ringers (BRS) group or the normal saline (NS) group. The primary outcomes were the incidence and severity of acute kidney injury after liver transplantation. The secondary outcomes included the rate of renal replacement therapy, length of mechanical ventilation, stay in the ICU, stay in the hospital after surgery and 30-day mortality. Other outcomes included the concentration of sodium, chloride, bicarbonate, anion gap, lactate concentration and changes in chloride preoperatively and postoperatively. Result: Sixty-two patients completed the trial and were analyzed, with 31 patients in each group. There was a significantly lower rate of postoperative acute kidney injury in the BRS group (14/31, 45.2%) than in the NS group (24/31, 77.4%), with a relative risk of 0.58 (95% CI, 0.38–0.90; p = 0.009). The severity of AKI in the BRS group was lower than that in the NS group (Z = -2.932, p = 0.003). There was no significant difference observed in the secondary outcomes. For other outcomes, the concentration of preoperative sodium was lower than postoperative sodium in the NS group (137.2 vs. 140.4, p = 0.009). The concentration of preoperative chloride was lower than that of postoperative chloride in the NS group (102.9 vs. 106.2, p < 0.001). The change in the concentration of chloride in the BRS group was lower than that in the NS group (1.6 vs. 4.7, p = 0.006). Conclusion: Sodium bicarbonate Ringer’s solution reduced the incidence and severity of acute kidney injury after classic orthotopic liver transplantation.

Can delayed grafting of frozen teeth achieve periodontal ligament healing?

Autologous teeth transplanted technology is putting healthy teeth into empty alveolar socket and waiting to be fixed by newly formed alveolar bone and periodontal membrane, to perform chewing function. Vigorous donor teeth are usually impacted teeth or orthodontic excess teeth that are often extracted and discarded during adolescence. However, they should have more potential function that repairing dentition defects due to caries, apical periodontitis, cysts, and other causes after being an adult. Therefore, once the preserved technical is skilled, utilization of dental tissues extracted early in life would create new possibilities. The problem is whether cryopreservation reduces tissue regeneration. Scholars who emphasize periodontal ligament (PDL) healing firmly believe it can avoid pathological reaction and ensure the success of transplantation. Nowadays, the ideal success rate can reach 80.0 % – 91.1%, but the classic transplantation procedure is time-dependent, which requires the donor tooth to be extracted and transplanted immediately. Freezing is a recognized effective way to make physiological and biochemical activities quiescent, and to maintain the potential of cells to relive after rewarming in the same medium. During cells cryopreservation, the challenge is in the inappropriate freezing and thawing condition, intracellular freezing would break cells’ physical structure, spoil normal PDL and increase resorption of root. So even though delay in freezing autotransplantation would greatly expand procedure indications, it has not yet become a mainstream treatment. Slow freezing and vitrification technology are main cryopreservation ways certified effective that essentially prevent ice crystals from damaging cells. To some extent, none of them is perfect considering cell cytotoxicity from cryoprotectants or controlling of freezing rate. Now, with the modified freezing method, we firstly put forward Antifreeze proteins (AFPs) to tooth cryopreservation, and assume that low concentration AFPs combined with vitrification may yield better results in PDL healing of delayed autotransplanted tooth. Based on analyzing the freezing mechanism, cell studies, animal experiments and individual case reports, we propose a procedural freezing method and summarized how to reduce cryogenic injury of cryopreserved tooth for potential use in tooth transplantation. However, more studies and data are needed about masticatory function and long-term prognosis observation.

Living donor kidney paired exchange: An observational study

BackgroundKidney transplantation is the treatment of choice for patients with end-stage renal disease (ESKD). Kidney paired donation (KPD) provides the chance to match an incompatible donor/recipient pair with another donor and recipient in a similar condition. We aimed to compare the outcomes of pair exchange kidney transplantation with traditional live donor kidney transplantation in our context. MethodA review of medical records of 62 patients (31 pairs) who underwent two-way conventional living kidney pair exchange from July 2016 to June 2021 was done. The control group was considered those 62 patients who had undergone classic live donor kidney transplantation (LDKT) during the study period. The patient's demographics, intraoperative and postoperative variables including delayed graft function, length of hospital stay, graft survival, patient survival, and rejections rates were compared between the groups (KPD and LDKT). ResultsThe majority of recipients were male (77.4 and 80.6%) while donors were female (77.4 and 69.4%) in KPD and the LDKT groups. Mean ages were 37 years (range: 19–59) and 37 years (range: 17–65) for the recipient's in KPD and the LDKT. KPD transplantation was performed in 62 recipients to avoid blood group incompatibility. There were no significant differences in outcomes comprising delayed graft function (1.6 and 3.2%), graft survival (100% in both groups), patient survival (95.2 and 96.8%), and rejections rates (1.6 and 1.6%) between KPD and LDKT group (P > 0.005). The length of stay was similar (5.9 and 5.7 days) in KPD and LDKT groups (P > 0.005). ConclusionsThe outcomes of KPD were comparable with classic LDKT in terms of delayed graft function, length of hospital stay, graft survival, patient survival, and rejections rates in our study. Therefore, the kidney paired donation program should be encouraged and promoted in centers where the ABO-incompatible transplant is expensive with added risk and the rate of deceased donor transplantation is very low.

Veno-Arterial Extracorporeal Membrane Oxygenation for Patients Undergoing Heart Transplantation: A 7-Year Experience.

Objective: Primary graft dysfunction (PGD) is the leading cause of early death after heart transplantation. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide temporary mechanical circulatory support and time for functional recovery of the transplanted heart. The purpose of this study was to analyze the timing and prognoses of VA-ECMO in patients with severe PGD after heart transplantation.Methods: A total of 130 patients underwent heart transplantation at the Zhongshan Hospital Affiliated with Fudan University between January 2014 and December 2020. All patients received basiliximab immunoinduction and a classic double vena cava anastomosis orthotopic heart transplantation. Among them, 29 patients (22.3%) developed severe PGD in the early postoperative period. VA-ECMO was performed in patients with difficulty weaning from cardiopulmonary bypass (CPB) or postoperative refractory cardiogenic shock. Patients were divided into two groups according to whether or not they were successfully weaned from VA-ECMO (patients who survived for 48 h after weaning and did not need VA-ECMO assistance again). The perioperative clinical data were recorded, and all patients were followed up until discharge. Early outcomes were compared between groups.Results: A total of 29 patients with VA-ECMO support after heart transplantation were included in this study. The proportion of patients receiving VA-ECMO was 22.3% (29/130). Nineteen patients (65.5%) needed VA-ECMO due to difficulty with weaning from CPB, and 10 patients required VA-ECMO for postoperative cardiogenic shock. Nineteen patients (65.5%) were successfully weaned from VA-ECMO. Overall, in-hospital mortality of VA-ECMO support patients was 55.2%. The main causes of death were ventricular fibrillation (four cases), major bleeding (three cases), infection (four cases), and graft failure (five cases).Conclusion: Despite advances in heart transplantation, severe PGD remains a lethal complication after heart transplantation. At present, the treatment for severe PGD after heart transplantation is a challenge. VA-ECMO provides an effective treatment for severe PGD after heart transplantation, which can promote graft function recovery.

Comparison of different parathyroid autograft project after total parathyroidectomy in patients with secondary hyperparathyroidism

ObjectiveTo evaluate the feasibility and efficacy of total parathyroidectomy followed by modified needle-quantified injection of parathyroid autograft compared with classic incision and transplantation. MethodsWe conducted a retrospective study of 171 patients with secondary hyperparathyroidism treated by hemodialysis or peritoneal dialysis. These patients were included in our study from April 2006 to December 2016, who had undergone total parathyroidectomies with autotransplantation. Patients were divided into classic incision for transplantation of parathyroid autograft group and modified needle-quantified injection group. Clinical and biochemical characteristics, including preoperative and postoperative intact parathyroid hormone levels were recorded and compared between two group patients. ResultsTo compare the techniques of modified needle-quantified injection and classic incision and transplantation, pre- and postoperative biochemistry and length of operation was recorded and analyzed. Preoperative biochemistry was similarly in both groups. However, autograft function achieved was significantly faster in the group with modified needle-quantified injection compared with classic incision and transplantation (P = 0.03). Median time to parathyroid function regain was 3 months for injection compared with 7 months for classic incision. There was no remarkable difference in the recurrence rates between the two groups. ConclusionThe modified needle-quantified injection of parathyroid tissue is a feasible and simple alternative to the more commonly used method of classic incision and transplantation.

Expression of putative leukemia stem cell targets in genetically-defined acute myeloid leukemia subtypes

Although most acute myeloid leukemia (AML) patients achieve complete remissions, the majority still eventually relapse and die of their disease. Rare primitive leukemia cells, so-called leukemia stem cells (LSCs), represent one potential type of resistant cell subpopulation responsible for this dissociation between response and cure. Several LSC targets have been described, but there is limited evidence about their relative utility or that targeting any can prevent relapse. LSCs not only appear to be biologically heterogeneous, but the classic immunocompromised mouse transplantation model also has serious shortcomings as an LSC assay. Out data suggest that the most immature cell phenotype that can be identified within a patient’s leukemia may be clinically relevant and represent the de facto LSC. Moreover, although phenotypically heterogeneous, these putative LSCs show consistent phenotypes within individual genetically defined groups. Using this LSC definition, we studied several previously described putative LSC targets, CD25, CD26, CD47, CD96, CD123, and CLL-1, and all were expressed across heterogeneous LSC phenotypes. In addition, with the exception of CD47, there was at most low expression of these targets on normal hematopoietic stem cells (HSCs). CD123 and CLL-1 demonstrated the greatest expression differences between putative LSCs and normal HSCs. Importantly, CD123 monoclonal antibodies were cytotoxic in vitro to putative LSCs from all AML subtypes, while showing limited to no toxicity against normal HSCs and hematopoietic progenitors. Since minimal residual disease appears to be a more homogeneous population of cells responsible for relapse, targeting CD123 in this setting may be most effective.

The effect of radiation on the ability of rat mammary cells to form mammospheres.

As classical transplantation repopulation assays for studying the radiobiology of rat mammary stem/progenitor cells are extremely time-consuming, this study aimed to characterize the radiobiological properties of mammospheres, spherical clumps of mammary cells formed under non-adherent culture conditions, which are a simple and widely used technique for assessing progenitor cell activity. Rat mammary cells were dissociated and used in transplantation repopulation assays and for the formation of mammospheres. Immunofluorescence for cytokeratin 14 and 18 was used to identify basal and luminal mammary epithelial cells, respectively. Incorporation of 5-bromo-2'-deoxyuridine was used to evaluate cell proliferation. The repopulating activity of the transplanted primary rat mammary cells demonstrated their radiosensitivity, reproducing previous data, with a significant reduction in repopulating activity at ≥ 2Gy. Cells constituting rat mammospheres were positive for either cytokeratin 14 or 18, with occasional double-positive cells. Both proliferation and aggregation contributed to sphere formation. Cells obtained from the spheres showed lower repopulating activity after transplantation than primary cells. When primary cells were irradiated and then used for sphere formation, the efficiency of sphere formation was significantly decreased at 8Gy but not at ≤ 6Gy, indicating radioresistance of the formation process. Irradiation at 8Gy reduced the proliferation of cells during sphere formation, whereas the cellular composition of the resulting spheres was unaffectes. Thus, mammosphere formation assays may measure a property of putative mammary progenitors that is different from what is measured in the classic transplantation repopulation assay in radiobiology.

Avian Pigment Pattern Formation: Developmental Control of Macro- (Across the Body) and Micro- (Within a Feather) Level of Pigment Patterns.

Animal color patterns are of interest to many fields, such as developmental biology, evolutionary biology, ethology, mathematical biology, bio-mimetics, etc. The skin provides easy access to experimentation and analysis enabling the developmental pigment patterning process to be analyzed at the cellular and molecular level. Studies in animals with distinct pigment patterns (such as zebrafish, horse, feline, etc.) have revealed some genetic information underlying color pattern formation. Yet, how the complex pigment patterns in diverse avian species are established remains an open question. Here we summarize recent progress. Avian plumage shows color patterns occurring at different spatial levels. The two main levels are macro- (across the body) and micro- (within a feather) pigment patterns. At the cellular level, colors are mainly produced by melanocytes generating eumelanin (black) and pheomelanin (yellow, orange). These melanin-based patterns are regulated by melanocyte migration, differentiation, cell death, and/or interaction with neighboring skin cells. In addition, non-melanin chemical pigments and structural colors add more colors to the available palette in different cell types or skin regions. We discuss classic and recent tissue transplantation experiments that explore the avian pigment patterning process and some potential molecular mechanisms. We find color patterns can be controlled autonomously by melanocytes but also non-autonomously by dermal cells. Complex plumage color patterns are generated by the combination of these multi-scale patterning mechanisms. These interactions can be further modulated by environmental factors such as sex hormones, which generate striking sexual dimorphic colors in avian integuments and can also be influenced by seasons and aging.

Potential benefits of modified corneal tissue grafts for keratoconus: Bowman layer 'inlay' and 'onlay' transplantation, and allogenic tissue ring segments.

Keratoconus can be surgically challenging, especially in advanced cases. Classic corneal transplantation techniques, may often be associated with complications. New alternative procedures like isolated Bowman layer transplantation (as a corneal stromal inlay or as a corneal onlay) and corneal allogenic intrastromal ring segments (CAIRS) have recently shown promising results. The aim of this review is to describe the main new surgical developments for treating keratoconus. Intrastromal Bowman layer transplantation has recently shown to be effective in halting keratoconus progression and maintaining visual acuity with contact lenses, at least up to 5-7 years postoperatively. Because intrastromal dissection can be challenging, we have recently developed a technique that allows using Bowman layer grafts as an onlay, that is positioned onto the patient's anatomical Bowman layer or anterior stroma, achieving comparable results as with Bowman layer inlay transplantation. CAIRS may also be an effective treatment, improving visual acuity, corneal surface parameters and keratoconus progression. There are currently some new alternative treatments such as isolated Bowman layer inlay or onlay transplantation and CAIRS, both of which seem effective at treating keratoconus and which may offer a less invasive surgical approach.

Does lobar or size-reduced lung transplantation offer satisfactory early and late outcomes?

A best evidence topic was constructed according to a structured protocol. The question addressed was whether size-reduced or lobar lung transplantation (LLTx) offers the same benefit as classic lung transplantation (LTx). Of the 147 papers found using the reported search, 9 were selected to provide the best evidence. Details of the studies regarding authors, date, journal, country of publication, study type, group studied, relevant outcomes and results are given. All studies reported survival rates of LLTx and most compared it with classical LTx. No statistical differences were reported in medium term and long term. Two of the studies reported a higher incidence of postoperative complications, such as the need for cardiopulmonary bypass, reperfusion oedema or primary graft dysfunction, and longer intubation or intensive care unit stay times. Although the largest study showed a significantly worse 1-year survival in LLTx, a sub-analysis considering patients successfully discharged showed similar outcomes at 1, 3 and 5 years when compared with classic LTx patients. We conclude that LLTx is a valid therapeutic option for recipients with significant donor size mismatch, offering similar outcomes as classical LTx in the medium term and long term.

Zebrafish Models of Cancer-New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate.

Zebrafish (Danio rerio) is a valuable non-mammalian vertebrate model widely used to study development and disease, including more recently cancer. The evolutionary conservation of cancer-related programs between human and zebrafish is striking and allows extrapolation of research outcomes obtained in fish back to humans. Zebrafish has gained attention as a robust model for cancer research mainly because of its high fecundity, cost-effective maintenance, dynamic visualization of tumor growth in vivo, and the possibility of chemical screening in large numbers of animals at reasonable costs. Novel approaches in modeling tumor growth, such as using transgene electroporation in adult zebrafish, could improve our knowledge about the spatial and temporal control of cancer formation and progression in vivo. Looking at genetic as well as epigenetic alterations could be important to explain the pathogenesis of a disease as complex as cancer. In this review, we highlight classic genetic and transplantation models of cancer in zebrafish as well as provide new insights on advances in cancer modeling. Recent progress in zebrafish xenotransplantation studies and drug screening has shown that zebrafish is a reliable model to study human cancer and could be suitable for evaluating patient-derived xenograft cell invasiveness. Rapid, large-scale evaluation of in vivo drug responses and kinetics in zebrafish could undoubtedly lead to new applications in personalized medicine and combination therapy. For all of the above-mentioned reasons, zebrafish is approaching a future of being a pre-clinical cancer model, alongside the mouse. However, the mouse will continue to be valuable in the last steps of pre-clinical drug screening, mostly because of the highly conserved mammalian genome and biological processes.

Effects of retrograde reperfusion on the intraoperative internal environment and hemodynamics in classic orthotopic liver transplantation

BackgroundTo investigate the effects of retrograde reperfusion on the intraoperative internal environment and hemodynamics in classic orthotopic liver transplantation (OLT).MethodsThirty patients were undergone classic OLT using retrograde reperfusion in our center. Blood sampling was done at different time points including: Before blood venting via the portal vein (PV), 10 mL of blood was collected from the inferior vena cava (T0); During retrograde reperfusion through the inferior vena cava (IVC), 10 mL of blood was collected when the volume of blood venting reached 10 mL (T1), 100 mL (T2), and 200 mL (T3), respectively. 5 mL of blood was analyzed using a NOVA-f–type Blood Gas Analyzer. The remaining 5 mL was measured to determine the level of IL-1β using an enzyme-linked immunosobent assay.ResultsAll operations were completed successfully, and postreperfusion syndrome (PRS) occurred in 6 patients (20%). The most notable findings were significant changes at T1, T2 and T3, including pH value, PvO2, SvO2, BEecf, HCO3−, Lac, K+, Ca2+ and IL-1β, compared with T0 (P < 0.05). Yet their levels at T3 were not back to the level at T0 (P < 0.05).ConclusionThis retrograde perfusion could eliminate some harmful metabolites inside the donor liver in time and reduce acid-base and electrolyte disorders as well as drastic hemodynamic fluctuations after recirculation during classic OLT.

Endoscopic Islet Autotransplantation Into Gastric Submucosa—1000-Day Follow-up of Patients

BackgroundTotal pancreatectomy and autologous transplantation of pancreatic islets is a treatment option for patients with severe pain due to chronic pancreatitis. In the standard procedure, pancreatic islets are isolated and subsequently administered into the portal vein. In the case of patients with a history of thrombosis or at risk of thrombosis, this route of administration is not viable. Animal studies conducted in our department led to the development of a technique of endoscopic islets transplantation into the gastric submucosa. In 2013 and 2014, the first human autologous transplant procedures were performed. The objective of this study was to present the results of a 3-year follow-up of these patients. MethodsTwo pancreatectomies were performed in our department, the first in 2013 and another in 2014, along with subsequent autologous transplantation of pancreatic islets into the gastric submucosa. ResultsBoth patients had been diagnosed previously with diabetes, and both had endogenous islet activity detected. Peptide C concentration after pancreatectomy and before pancreatic cell transplantation was 0.1 ng/mL. After the transplantation, peptide C concentrations for the 2 patients were 0.8 and 0.5 ng/mL on day 7, 1.2 and 0.6 ng/mL on day 30, 1.3 and 0.8 ng/mL on day 180, 1.1 and 0.7 ng/mL on day 360, and 3.0 and 0.6 ng/mL at 3 years, respectively, after transplantation. The pain symptoms resolved in both cases. ConclusionPancreatic islets may survive in the gastric wall. Endoscopic submucosal transplantation may present an alternative for the management of patients who cannot undergo a classic transplantation procedure.

Clinical outcomes in liver transplantation from donation after cardiac death

Objective To investigate the clinical outcomes in liver transplantation from donation after cardiac death (DCD) . Methods The clinical data of 52 patients with end stage liver disease who received liver transplantation from DCD donors (the age of 21 pediatric recipients <18 years, and the age of 31 adult recipients≥18 years) at the Tianjin First Central Hospital from December 2008 to July 2013 were retrospectively analyzed. The intraoperative, postoperative and prognosis data were analyzed. All patients were regularly followed up in the Transplantation Follow-up Center after discharge till July 31 , 2014. The measurement data with normal distribution were presented as±s. The comparison between groups was evaluated with the repeated measures ANOVA. The cumulative survival rate was done by the Kaplan-Meier method. Results Among the 21 pediatric recipients, 16 received classic orthotopical liver transplantation and 5 received reduced-size liver transplantation from adult donors. The weight of 21 DCD livers, graft to recipient weight ratio (GRWR) , warm ischemia time, cold ischemia time, anhepatic phase, volume of intravenous infusion, operation time and volume of intraoperative blood loss were (338±34) g, 1. 9%±0. 7% , (16±6) minutes, (86±36) minutes, (43±10) minutes, (816±662) mL, (7. 1 ± 1. 5) hours and (329±214) mL, respectively. No peritoneal effusion, acute cellular rejection (ACR) , portal vein thrombosis (PVT) and biliary complications occurred in the pediatric recipients. The duration of hospital stay was (41±23) days. The level of hemoglobin (Hb) and albumin (Alb) to reach the normal level from pre-operation to postoperative day 14 were (101±19) g/ L to (128±23) g/ L and (34±7) g/L to (44±7) g/ L, respectively, with significant differences (F =3.943 , 7.340, P <0.05) . The level of total bilirubin (TBil) , aspartate transaminase (AST) and alanine transaminase (ALT) gradual reducing to the normal level from preoperation to postoperative day 14 were (307±69) μmol/ L to (34±17) μmol/ L, (88±34) U/ L to (36±17) U/ L and (154±51) U/ L to (46±18) U/ L, respectively, with significant differences (F =142.200, 17.060, 31.750, P <0.05) . Thirtyone adult recipients received classic orthotopical liver transplantation form adult donors. The weight of 21 DCD livers, GRWR, warm ischemia time, cold ischemia time, anhepatic phase, volume of intravenous infusion, operation time and volume of blood loss were (1 104 ± 43) g, 1. 7% ± 0. 4%, (16 ± 4) minutes, (89 ± 43) minutes, (47±9) minutes, (2 515±1 803) mL, (7. 9 ± 1.8) hours and (1 208 ± 548) mL, respectively. The complications occurred in 14 adult recipients, including peritoneal effusion in 8 recipients, ACR in 3 recipients, PVT in 2 recipients and biliary complications in 1 recipient. The duration of hospital stay was (44±22) days. The level of Alb to reach the normal level from pre-operation to postoperative day 14 were (31±5) g/ L to (40±5) g/ L, with a significant difference (F =14.930, P <0.05) . The level of TBil, AST and ALT gradual reducing to the nearly normal level from pre-operation to postoperative day 14 were (182 ± 55) μmol/ L to (62 ± 22) μmol/ L, (286 ± 93) U/ L to (79±47) U/ L and (349±111) U/ L to (76±28) U/ L, respectively, with significant differences (F = 34.350, 71.070, 82.680, P <0.05) . All the 52 recipients were followed up for a median time of 544 days (range, 196-1 953 days) , with 1-year survival rate of 90.38%. During the follow-up, 1 pediatric recipient died of pulmonary infection and 1 of massive hemorrhage, and 1 adult recipient died of pulmonary infection, 1 of primary graft dysfunction and 1 of massive hemorrhage. Conclusion Liver transplantation from DCD is a feasible treatment for end-stage liver diseases, with a good short-term clinical outcomes. Key words: End stage liver disease; Donation after cardiac death; Liver transplantation; Short-term outcomes; Clinical analysis

Graft versus host disease following liver transplantation: A case report.

Graft versus host disease (GVHD) is an uncommon complication following liver transplantation. In the present case report, a 53-year-old male hepatitis B virus carrier was diagnosed with primary liver cancer with post-hepatitis cirrhosis. Preoperative cytomegalovirus (CMV), Epstein-Barr virus, coxsackievirus, herpes simplex virus and autoimmune antibody series were negative. Preoperative human leukocyte antigen type was also negative. Following classic orthotropic liver transplantation, postoperative treatment included immunosuppression therapy, infection protection, anti-human immunodeficiency virus therapy and CMV infection protection therapy. Chemotherapy was initiated at day 16 following surgery. At day 26 following the transplantation, the patient developed a fever of unknown cause, and a scattered red rash was observed behind the left ear and on the neck. The patient presented with a fever of unknown cause, rash, symptoms of the digestive tract, leukocytopenia and pancytopenia. A diagnosis of GVHD was confirmed following a skin biopsy. Symptomatic therapies, including antivirals, anti-anaphylaxis drugs and steroids were administered. However, the patient succumbed to infection, acute respiratory distress syndrome and multiple organ failure at day 46 following surgery. Therefore, an effective therapeutic strategy for the treatment of GVHD following liver transplantation is yet to be established, and further research is required prior to such a regimen being developed.

Nonhuman Primate Lung Decellularization and Recellularization Using a Specialized Large-organ Bioreactor

There are an insufficient number of lungs available to meet current and future organ transplantation needs. Bioartificial tissue regeneration is an attractive alternative to classic organ transplantation. This technology utilizes an organ's natural biological extracellular matrix (ECM) as a scaffold onto which autologous or stem/progenitor cells may be seeded and cultured in such a way that facilitates regeneration of the original tissue. The natural ECM is isolated by a process called decellularization. Decellularization is accomplished by treating tissues with a series of detergents, salts, and enzymes to achieve effective removal of cellular material while leaving the ECM intact. Studies conducted utilizing decellularization and subsequent recellularization of rodent lungs demonstrated marginal success in generating pulmonary-like tissue which is capable of gas exchange in vivo. While offering essential proof-of-concept, rodent models are not directly translatable to human use. Nonhuman primates (NHP) offer a more suitable model in which to investigate the use of bioartificial organ production for eventual clinical use. The protocols for achieving complete decellularization of lungs acquired from the NHP rhesus macaque are presented. The resulting acellular lungs can be seeded with a variety of cells including mesenchymal stem cells and endothelial cells. The manuscript also describes the development of a bioreactor system in which cell-seeded macaque lungs can be cultured under conditions of mechanical stretch and strain provided by negative pressure ventilation as well as pulsatile perfusion through the vasculature; these forces are known to direct differentiation along pulmonary and endothelial lineages, respectively. Representative results of decellularization and cell seeding are provided.