Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro.

Unlabelled: : Bone marrow mesenchymal stromal cells (BM-MSCs) have been characterized and used in many clinical studies based on their immunomodulatory and regenerative properties. We have recently reported the benefit of autologous MSC systemic therapy in the treatment of type 1 diabetes mellitus (T1D). Compared with allogeneic cells, use of autologous products reduces the risk of eliciting undesired complications in the recipient, including rejection, immunization, and transmission of viruses and prions; however, comparable potency of autologous cells is required for this treatment approach to remain feasible.

Pre-transplant donor-specific anti-human leukocyte antigen antibodies are associated with high risk of delayed graft function after renal transplantation.

Background: Sensitive screening methods have revealed that many patients have donor-specific human leucocyte antigen antibodies (DSAs) prior to transplantation, regardless of negative crossmatch results. The clinical significance of pre-transplant (pre-Tx) DSAs for early graft function has remained unclear. Our aim was to examine the association of DSAs with delayed graft function (DGF).

Serum neutrophil gelatinase-associated lipocalin and recovery of kidney graft function after transplantation.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a marker for acute kidney injury. We studied whether serum NGAL predicts delayed graft function (DGF) and recovery of kidney function after transplantation.

Methods: Serum NGAL was analyzed using commercial ELISA and point-of-care (POC) (Triage®, Biosite) methods.

Pretransplant dialysis duration and risk of death after kidney transplantation in the current era.

Background: Although longer pretransplant dialysis has been associated with poor kidney transplant outcome, no data about this association exist from the current era or from Europe. We studied the association of pretransplant dialysis duration on outcomes after kidney transplantation across two different time periods.

Methods: All recipients of first kidney transplantation between 1990 and 2010 in Finland were included (N=3,105) in this observational follow-up study of an inception cohort.

Adenine phosphoribosyltransferase deficiency as a rare cause of renal allograft dysfunction.

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder manifesting as urolithiasis or crystalline nephropathy. It leads to the generation of large amounts of poorly soluble 2,8-dihydroxyadenine excreted in urine, yielding kidney injury and in some patients, kidney failure. Early recognition of the disease, institution of xanthine analog therapy to block the formation of 2,8-dihydroxyadenine, high fluid intake, and low purine diet prevent CKD.

[Kidney transplantation from a living donor: criteria for donor and recipient].

The annual number of kidney transplantations in Finland is 150 to 200. Successful kidney transplantation improves the patient's quality of life and prognosis and is cost-effective as compared with dialytic therapy. Only a few per cent of transplantations are made from a living donor.

BK virus viremia in a well-HLA-matched kidney transplant population mainly on low-dose cyclosporine-based immunosuppression.

The incidence and clinical course of polyomavirus-associated nephropathy (PyVAN) in our well-HLA-matched kidney transplant population mainly on low-dose cyclosporine-based triple-drug immunosuppression has not been described in detail. We aimed to characterize our patients with PyVAN and BK virus (BKV) viremia. Among 166 kidney transplantations between January 2007 and February 2011 followed up at Helsinki University Hospital nephrology clinic, 136 were screened for BKV viremia by quantitative analysis of BKV DNA in plasma.

On the etiology of type 1 diabetes: a new animal model signifying a decisive role for bacteria eliciting an adverse innate immunity response.

The cause of type 1 diabetes (T1D) remains unknown; however, a decisive role for environmental factors is recognized. The increased incidence of T1D during the last decades, as well as regional differences, is paralleled by differences in the intestinal bacterial flora. A new animal model was established to test the hypothesis that bacteria entering the pancreatic ductal system could trigger β-cell destruction and to provide new insights to the immunopathology of the disease.

Tacrolimus-based, steroid-free regimens in renal transplantation: 3-year follow-up of the ATLAS trial.

Background: Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects.

Methods: This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study.

HHV-6B is frequently found in the gastrointestinal tract in kidney transplantation patients.

In immunosuppressed patients human herpesvirus 6 (HHV-6) reactivations are common. The aim of the study was to determine to which extent HHV-6 can be found in the gastrointestinal tract in kidney transplant recipients and in patients on chronic dialysis. The HHV-6 and cytomegalovirus (CMV) examinations were performed on gastro duodenal and colon biopsy specimens obtained from 81 kidney transplant recipients and on 46 chronic dialysis patients.

Using HTK for prolonged pancreas preservation prior to human islet isolation.

Background: Histidine-tryptophan-ketoglutarate (HTK) has been established as an alternative to University-of-Wisconsin solution (UWS) for abdominal organ preservation, but data about HTK efficiency to preserve pancreata during prolonged cold ischemia time (CIT) are conflicting. In human islet transplantation, HTK provided similar isolation outcomes after short CIT. The present study aimed to investigate whether islets can be successfully isolated from HTK-preserved pancreata after prolonged CIT compared with UWS.

Deceased donor neutrophil gelatinase-associated lipocalin and delayed graft function after kidney transplantation: a prospective study.

Introduction: Expanding the criteria for deceased organ donors increases the risk of delayed graft function (DGF) and complicates kidney transplant outcome. We studied whether donor neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker for acute kidney injury, could predict DGF after transplantation.

Methods: We included 99 consecutive, deceased donors and their 176 kidney recipients.

Posttransplant sCD30 as a predictor of kidney graft outcome.

Background: Reliable markers for assessing the biological effect of immunosuppressive drugs and identification of transplant recipients at risk of developing rejection are not available.

Methods: In a prospective multicenter study, we investigated whether posttransplant measurement of the T-cell activation marker soluble CD30 (sCD30) can be used for estimating the risk of graft loss in kidney transplant recipients. Pre- and posttransplant sera of 2322 adult deceased-donor kidney recipients were tested for serum sCD30 content using a commercial enzyme-linked immunosorbent assay.

Donor risk score and baseline biopsy CADI value predict kidney graft outcome.

Different donor parameters and baseline biopsy have been used to assess the quality of donor organs. There is, however, no consensus which risk factors and chronic changes in the donor kidney can be accepted for transplantation. The study included 481 deceased organ donors and their 829 kidney recipients transplanted during 1995-2005.

[Kidney transplantation criteria in Finland].

In the treatment of end-stage renal disease, kidney transplantation is the best and most cost-effective alternative with regard to both prognosis and quality of life. Problems arise from the disproportion between the number of available allografts and the patients waiting for the transplantation. There are few absolute contraindications to kidney transplantation.

Urine neutrophil gelatinase-associated lipocalin is a marker of graft recovery after kidney transplantation.

Delayed graft function (DGF), especially long-lasting DGF, complicates kidney transplant outcome. Neutrophil gelatinase-associated lipocalin (NGAL) is an acute kidney injury marker; therefore, we tested whether urine NGAL could predict DGF, prolonged DGF (lasting over 14 days), or the quality of kidney function in transplant recipients without DGF (non-DGF). We collected urine samples from 176 recipients transplanted with deceased donor kidneys before and various days after transplantation.

Collecting high-quality pancreatic tissue for experimental study from organ donors with signs of β-cell autoimmunity.

Background: The aim of this study was to create a new research strategy to obtain high-quality pancreatic tissues from subjects with preclinical or clinical type 1 diabetes, which would open up new avenues for studying the mechanisms of the β-cell damaging process in humans.

Research Design And Methods: A nationwide collaboration network (the PanFin network) was established in Finland to start an on-call screening of diabetes-associated autoantibodies from deceased organ donors and subsequent processing of pancreases from autoantibody-positive donors. This protocol was integrated into the national organ transplantation procedure.

A new oxygen carrier for improved long-term storage of human pancreata before islet isolation.

Background: Pancreas oxygenation during cold storage has been established in islet isolation and transplantation to prevent ischemic tissue damage using perfluorodecalin (PFD) as hyperoxygen carrier. However, studies in humans and pigs provided conflicting results about the efficiency of PFD for pancreas oxygenation. The aim of this study was to compare PFD with a newly developed oxygen carrier composed of perfluorohexyloctane and polydimethylsiloxane 5 (F6H8S5) for long-term storage of human pancreata.

Tacrolimus combined with two different corticosteroid-free regimens compared with a standard triple regimen in renal transplantation: one year observational results.

Side effects of steroid use have led to efforts to minimize their use in transplantation. Two corticosteroid-free regimens were compared with a triple immunosuppressive therapy. Data from the original intent-to-treat (ITT) population (153 tacrolimus/basiliximab [Tac/Bas], 151 tacrolimus/MMF [Tac/MMF], and 147 tacrolimus/MMF/steroids [control]) were analyzed in a 12-month follow-up.

Vitronectin receptors, alpha v integrins, are recognized by several non-RGD-containing echoviruses in a continuous laboratory cell line and also in primary human Langerhans' islets and endothelial cells.

Previously published data suggest that the RGD-recognizing integrin, alphavbeta3, known as the vitronectin receptor, acts as a cellular receptor for RGD-containing enteroviruses, coxsackievirus A9 (CAV-9) and echovirus 9 (E-9), in several continuous cell lines as well as in primary human Langerhans' islets. As this receptor is also capable of binding the ligands by a non-RGD-dependent mechanism, we investigated whether vitronectin receptors, alpha v integrins, might act as receptors for other echoviruses that do not have the RGD motif. Blocking experiments with polyclonal anti-alphavbeta3 antibody showed that both primary human islets and a continuous laboratory cell line of green monkey kidney origin (GMK) are protected similarly from the adverse effects of several non-RGD-containing echovirus (E-7, -11, -25, -30, -32) infections.

CMV findings in the gastrointestinal tract in kidney transplantation patients, patients with end-stage kidney disease and immunocompetent patients.

Aim: Cytomegalovirus (CMV) is the most common viral pathogen affecting organ transplant recipients. The objective was to determine to what extent CMV can be found in the gastrointestinal tract in kidney transplant recipients and to compare them with patients in dialysis and randomly chosen otherwise healthy patients who were referred for oesophagogastroduodenoscopy (OEGD) or colonoscopy.

Patients And Methods: Biopsies for CMV examinations were obtained from 130 oesophagogastroduodenoscopies and 54 colonoscopies performed on 82 kidney transplant recipients, 49 dialysis patients with chronic end-stage kidney disease and 53 immunocompetent patients because of clinical indications.

Association of genetic variation in inducible costimulator gene with outcome of kidney transplantation.

Background: The closely-linked genes of CD28, cytotoxic T-lymphocyte associated antigen 4 (CTLA4), inducible costimulator (ICOS), and programmed cell death 1 on chromosome 2q encode costimulatory molecules, which are regulators of the T-cell activity. The T-cell mediated immune response has a major role in allograft rejection. Hence, the variation in these genes may have an effect on graft survival and the amount of immunosuppression needed, but so far the studies have restricted solely to the CTLA4 gene.

The importance of tryptic-like activity in purified enzyme blends for efficient islet isolation.

Background: The isolation of islets from the human pancreas critically depends on an efficient enzyme blend. Previous studies have solely focused on the presence of collagenase and neutral protease/thermolysin. Despite improved characterization of these components, the lot-related variability in efficacy still persists suggesting that additional so far disregarded enzymes are required for efficient islet cleavage.