Background: Hepatic interstitial T-lymphocytes (T-Li), Natural Killer (NK) and NK-T cells play an important role in both innate and adaptive immunity and contribute to the regulation of ischemia/reperfusion injury (IRI) after transplantation of abdominal organ. Methods: The cellular concentrations and phenotypes of NK, T-Li, NK-T were analyzed retrospectively in a consecutive series of hepatic perfusates after surgical removal of whole livers on the bench previously collected from adult multi-organ donors after brain death. (DBD), and compared with the demographic and pathological characteristics of the patients transplanted at our Institute with kidneys taken from the same donors. The liver interstitial cells were purified from the perfusate by density gradient centrifugation and the phenotype was determined by flow cytometric investigation using the following immunological markers: CD3, CD4, CD8 and CD56 in order to determine the relative percentage of T-Li, NK-T and NK cells. Results: The perfusates of 42 DBDs, and the related clinical outcome of kidney transplant recipients from 2010 to 2020, were analyzed. T-Li were significantly associated with the time in days of delayed functional recovery of transplanted kidneys (DGF) (p = 0.02), to onset of secondary infection from Cytomegalovirus (p = 0.03). On COX analysis, percent cell concentration of T-Li and time to DGF were significantly associated with an increased relative risk (HR) of organ survival (HR = 1.038, p = 0.04; and HR = 1.029, p = 0.01, respectively). The specificity of the NK and NK-T cell proportions were not associated with any relevant clinical outcomes in kidney transplant patients. Conclusions: The present study points to a new potential role of T-Li cells detected in the context of liver perfusate DBD, and could detect potential impacts in organ allocation, surgical harvesting techniques and in the analysis of IRI pathophysiological events after kidney transplants from multi-organ DBDs.

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multi-targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia–reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 hours of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cyto-kines, oxidative stress, gene expression of apoptosis-related genes, TNF-alpha and Caspase 3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the Caspase 3 protein and a reduction in the TNF-alpha protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes and their combination represent a promising therapeutic proposal against liver IRI.

Measuring the non-pathogenic Torque Teno Virus (TTV) load allows assessing the net immunosuppressive state after kidney transplantation (KTx). Currently, it is not known how exposure to maintenance immunosuppression affects TTV load. We hypothesized that TTV load is associated with the exposure to mycophenolic acid (MPA) and tacrolimus. We performed a prospective study including 54 consecutive KTx. Blood TTV load was measured by an in-house PCR at months 1 and 3. Together with doses and trough blood levels of tacrolimus and MPA, we calculate the coefficient of variability (CV), time in therapeutic range (TTR) and concentration/dose ratio (C/D) of tacrolimus, and the MPA-area under the curve (AUC-MPA) at the third month. TTV load at the first and third month discriminated those patients at risk of developing opportunistic infections between months 1 and 3 (AUC-ROC 0.723, 95%CI 0.559-0.905, p = 0.023) and between months 3 to 6 (AUC-ROC 0.778, 95%CI 0.599-0.957, p = 0.028), respectively, but not those at risk of acute rejection. TTV load did not relate to mean tacrolimus blood level, CV, TTR, C/D and AUC-MPA. To conclude, although TTV is a useful marker of net immunosuppressive status after KTx, it is not related to exposure to maintenance immunosuppression.

Recently, two pig-to-human kidney transplants and a pig-to-human heart transplant were completed. The kidney trials involved a patient who was deceased and a patient who was brain dead. They seemed to indicate that pig kidneys can be at least somewhat functional in humans. However, patients still have to be under severe immunosuppression - and the first patient to receive a porcine heart passed away after two months. It is difficult to know exactly which proteins we need to overexpress or underexpress/knockout in a porcine organ to negate the human recipient’s immunological response to it. And testing different porcine organ genetic modifications in baboons can cost around $500,000 per transplant. But there might be a way to decrease immunogenicity where we don’t have to worry so much about modifying the animal’s organs genetically. First, however, we would have to prevent complement factor-mediated lysis of the porcine vascular endothelial cells, which we have made much progress on with triple knockout animals. Then, we could modify the porcine organ so that the cells of said organ secrete a small molecule or peptide that acts as a chemorepellent for the host immune cells. The host immune cells can be modified via bone marrow transplant or vector delivery to express the chemorepulsion receptor.

Recently, two pig-to-human kidney transplants and a pig-to-human heart transplant were completed. The kidney trials involved a patient who was deceased and a patient who was brain dead. They seemed to indicate that pig kidneys can be at least somewhat functional in humans. However, patients still have to be under severe immunosuppression - and the first patient to receive a porcine heart passed away after two months. It is difficult to know exactly which proteins we need to overexpress or underexpress/knockout in a porcine organ to negate the human recipient’s immunological response to it. And testing different porcine organ genetic modifications in baboons can cost around $500,000 per transplant. But there might be a way to decrease immunogenicity where we don’t have to worry so much about modifying the animal’s organs genetically. First, however, we would have to prevent complement factor-mediated lysis of the porcine vascular endothelial cells, which we have made much progress on with triple knockout animals. Then, we could modify the porcine organ so that the cells of said organ secrete a small molecule or peptide that acts as a chemorepellent for the host immune cells. The host immune cells can be modified via bone marrow transplant or vector delivery to express the chemorepulsion receptor.

The human body is inhabited by unique microbial communities that protect and regulate the host against pathogens and inflammation. To address issues related to disrupted microbial composition, microbial transfer therapy (MTT) has emerged as a potential treatment option. The most popular form of MTT is fecal microbiota transplantation (FMT), which has been successful in treating various diseases. Another emerging form of MTT is vaginal microbiota transplantation (VMT), transferring of the vaginal microbiota from a healthy female donor to a diseased patient's vaginal cavity, which aims to restore normal vaginal microbial composition. However, VMT is vastly unexplored due to safety concerns and lack of research. This paper explores the mechanisms involved in VMT's therapeutic effect and discusses future perspectives. Further research is needed to advance VMT's clinical applications and techniques.

Background: COVID-19 infection has received the attention of the scientific community due its respiratory manifestations and association with evolution to severe acute respiratory syndrome (SARS-CoV-2). There are few studies characterizing SARS-CoV-2 in pediatric immunocompromised patients, such as liver transplanted (LT) patients.The aim of this study was to analyze the outcomes of the larger cohort of pediatric liver transplant recipients (PLTR) from a single center in Brazil who where contaminated with COVID-19 during the pandemic. Methods: Cross-sectional study. Primary outcomes: COVID-19 severity. The Cox regression method was used to determine independent predictors associated with the outcomes. Results: 74 PLTR were included. Patients were divided into two groups according to the severity of COVID-19 disease: moderate-severe COVID and asymptomatic-mild COVID. Patients categorized as moderate-severe COVID were younger (12.6 months vs. 82.1 months, p 0.03), higher prevalence of transplantation with deceased donor (50% vs. 4.3%, p 0.02) and with a higher prevalence of COVID-infected patients before 6 months after LT (75% vs. 5.7%, p 0.002). The independent predictor of COVID-19 severity identified in the multivariate analysis was COVID-19 infection < 6 months after LT (HR=0.001, 95% CI=0.001-0.67, p 0.03). Conclusion: The time interval of less than 6 months between COVID-19 infection and LT was the only predictor of disease severity in pediatric patients.

Background: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), acute leukemia relapse is common, and asymmetric bone marrow recurrence hasn’t been reported. Because the anatomical distribution of acute leukemia clones in the bone marrow after allo-HSCT is presumed to be diffuse, bone marrow aspirations are performed in single site. Case presentation: We identified two acute leukemia patients, whose leukemic burden in bilateral bone marrow specimens differed significantly. The first case was a 20-year-old man who was diagnosed with acute myelomonocytic leukemia and received haploidentical allo-HSCT. He had been in complete remission for two years and off immunosuppressive medications for a year, with normal peripheral blood count. Routine bone marrow biopsy of his left posterior iliac bone marrow showed 52% leukemia blasts, while the right side had 0% blasts ten days later. Due to the discordant results, the patient refused further intervention and died of high leukocyte syndrome four months later. The second case was a 23-year-old woman who was diagnosed with acute B lymphoblastic leukemia and received HLA-identical sibling allo-HSCT. Although 62% of blasts were found in her left iliac marrow on day +122, 0 % of blasts were found on a sample obtained from the right iliac crest on day +128. Whole-body 18F-FDG PET/CT scans confirmed that the leukemic infiltration in her bone marrow was asymmetric. Considering the higher leukemic burden on the left, we chose the left posterior iliac crest aspiration for further response evaluation. After chemotherapy combined with donor lymphocyte infusion, she achieved transient hematologic complete remission. She died of septic shock with heart failure at +258 days after allo-HSCT before infusion of anti-CD19 donor chimeric antigen receptor T cells. Conclusions: To our knowledge, these are the first case reports of asymmetric bone marrow infiltration of blasts in acute leukemia patients after allo-HSCT. Bilateral posterior iliac crest aspirations or 18F-FDG-PET/CT scans may help distinguish such distribution. If discordant bone marrow specimens are observed, physicians should restrict future bone marrow studies to the more involved side.

The shortage of donor organs is a major global concern. Organ failure requires the transplantation of functional organs. Organ donors are preserved in warm or cold ischemia. Ischemia and reperfusion damage the organs, due to the lack of oxygen during the ischemia step and the oxidative stress during the reperfusion step. Different methodologies were developed to prevent or diminish the level of injuries. Preservation solutions were first developed, followed by the addition of chemical compounds. In addition of inhibitors of mitogen activated protein kinase, inhibitors of the proteasome, mesenchymal stem cells started to be used 13 years ago to prevent or diminish the organ’s injuries. Mesenchymal stem cells (e.g bone marrow stem cells, adipose derived stem cells) have proven to be powerful tools in repairing damaged organs. This review will focus on the use of some bone marrow stem cells, adipose derived stem cells and umbilical cord stem cells on preventing or decreasing the injuries due to ischemia-reperfusion.

In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also has an interesting aspect as a mesenchymal stem cell reservoir. The splenic mesenchymal stem cells contribute to tissue repair in damaged tissue, and thus, the infusion can be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.