Search results for "Transplant"

Non-cognate bystander cytolysis by clonal epitope-specific CTL lines through CD28-CD80 interaction inhibits antibody production: A potential caveat t…

2015

Abstract Adoptive transfer of virus epitope-specific CD8 T cells is an immunotherapy option to control cytomegalovirus (CMV) infection and prevent CMV organ disease in immunocompromised solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) recipients. The therapy aims at an early, selective recognition and cytolysis of infected cells for preventing viral spread in tissues with no adverse immunopathogenic side-effects by attack of uninfected bystander cells. Here we describe that virus epitope-specific, cloned T-cell lines lyse target cells that present the cognate antigenic peptide to the TCR, but simultaneously have the potential to lyse uninfected cells expressing…

STAT1 Isoforms Differentially Regulate NK Cell Maturation and Anti-tumor Activity

2020

Natural killer (NK) cells are important components of the innate immune defense against infections and cancers. Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that is essential for NK cell maturation and NK cell-dependent tumor surveillance. Two alternatively spliced isoforms of STAT1 exist: a full-length STAT1α and a C-terminally truncated STAT1β isoform. Aberrant splicing is frequently observed in cancer cells and several anti-cancer drugs interfere with the cellular splicing machinery. To investigate whether NK cell-mediated tumor surveillance is affected by a switch in STAT1 splicing, we made use of knock-in mice expressing either only the STAT1α (S…

2017

Better identification of severe acute graft-versus-host disease (GvHD) may improve the outcome of this life-threatening complication of allogeneic hematopoietic stem cell transplantation. GvHD induces tissue damage and the release of damage-associated molecular pattern (DAMP) molecules. Here, we analyzed GvHD patients (n = 39) to show that serum heat shock protein glycoprotein 96 (Gp96) could be such a DAMP molecule. We demonstrate that serum Gp96 increases in gastrointestinal GvHD patients and its level correlates with disease severity. An increase in Gp96 serum level was also observed in a mouse model of acute GvHD. This model was used to identify complement C3 as a main partner of Gp96 i…

Stem cell therapy. Old challenges and new solutions

2020

Stem cell therapy (SCT), born as therapeutic revolution to replace pharmacological treatments, remains a hope and not yet an effective solution. Accordingly, stem cells cannot be conceivable as a "canonical" drug, because of their unique biological properties. A new reorientation in this field is emerging, based on a better understanding of stem cell biology and use of cutting-edge technologies and innovative disciplines. This will permit to solve the gaps, failures, and long-term needs, such as the retention, survival and integration of stem cells, by employing pharmacology, genetic manipulation, biological or material incorporation. Consequently, the clinical applicability of SCT for chro…

Wharton's Jelly Mesenchymal Stromal Cells as a Feeder Layer for the Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells: a Review

2016

In recent years, umbilical cord blood (UCB) has been widely used as an alternative source to bone marrow (BM) for transplantation of hematopoietic stem and progenitor cells (HSPCs) in a variety of hematological and non-hematological disorders. Nevertheless, the insufficient number of UCB-HSPCs for graft represents a major challenge. HSPCs ex vivo expansion prior to transplantation is a valid strategy to overcome this limit. Several attempts to optimize the expansion conditions have been reported, including the use of mesenchymal stromal cells (MSCs) as feeder layer. Wharton's Jelly (WJ), the main component of umbilical cord (UC) matrix, is especially rich in MSCs, which are considered ideal…

ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation

2016

Summary Huntington's disease (HD) is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor). By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA) chemical and two genetic HD mouse models (R6/2 and N171-82Q) on the basis of distinct behavioral parameters, including CatWalk gait analysis. Explicit rescue of motor function by…

Cirrhosis risk score of the donor organ predicts early fibrosis progression after liver transplantation.

2019

Background & Aims: Fibrosis progression (FP) after liver transplantation (LT) increases morbidity and mortality. Biomarkers are needed for early prediction of FP. A recipient’s seven-gene cirrhosis risk score (CRS) has been associated with FP, especially in non-transplant cohorts. A broader validation of CRS, including the genotype of the donor-organ and HCV-negative patients is lacking. We therefore analyzed the impact of donor- and recipient-specific genotypes on FP after LT in a large cohort of HCV-positive and -negative patients.Method: Genotyping from liver biopsies (n=201 donors) and peripheral blood (n=442 recipients) was performed. Cirrhosis risk score was correlated with FP at …

Treatment strategies for lysosomal storage disorders.

2017

Over the past several years the number of treatments available for patients with lysosomal storage disorders has rapidly increased. Haematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction, and chaperone therapies are currently available, and gene therapies and other treatments are rapidly advancing. Despite remarkable advances, the efficacy of most of these therapies is limited, particularly because the treatments are usually initiated when organ damage has already occurred. To circumvent this limitation, screening in newborn infants for lysosomal storage disorders has been introduced in many countries. However, this screening is complicated by the broad cl…

IL-17A mediated endothelial breach promotes metastasis formation

2015

Abstract The role of the IL23/IL17A axis in tumor–immune interactions is a matter of controversy. Although some suggest that IL17A-producing T cells (TH17) can suppress tumor growth, others report that IL17A and IL23 accelerate tumor growth. Here, we systematically assessed the impact of IL17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate mapping revealed that IL17A was secreted within lung metastases predominantly by γδ T cells, whereas TH17 cells were virtually absent. Using different tumor models, we found Il17a−/− mice to consistently develop fewer pulmonary tumor colonies. IL17A specifically increased blood vessel permeability and the expression …

Efficacy of interleukin 10 gene hydrofection in pig liver vascular isolated ‘in vivo’ by surgical procedure with interest in liver transplantation

2019

AIM Liver transplantation is the only curative strategy for final stage liver diseases. Despite the great advances achieved during the last 20 years, the recipient immune response after transplantation is not entirely controlled. This results in high rates of acute cell rejection and, approximately, 10% of early mortality. Therapeutic treatment could be improved by efficiently transfecting genes that encode natural immunosuppressant proteins, employing safe procedures that could be transferred to clinical setting. In this sense, interleukin 10 plays a central role in immune tolerance response by acting at different levels. METHODS hIL10 gene was hydrofected by retrograde hydrodynamic inject…