Search results for "Transplantation"

NOTCH3 expression is linked to breast cancer seeding and distant metastasis

2018

Background Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF…

2020

Abstract Background Stem cells` (SC) functional heterogeneity and its poorly understood aetiology impedes clinical development of cell-based therapies in regenerative medicine and oncology. Recent studies suggest a strong correlation between the SC migration potential and their therapeutic efficacy in humans. Designating SC migration as a denominator of functional SC heterogeneity, we sought to identify highly migrating subpopulations within different SC classes and evaluate their therapeutic properties in comparison to the parental non-selected cells. Methods We selected highly migrating subpopulations from mesenchymal and neural SC (sMSC and sNSC), characterized their features including b…

2021

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Measuring CMV-specific cellular immunity may improve the risk stratification and management of patients. IFN-γ ELISpot assays, based on the stimulation of peripheral blood mononuclear cells with CMV pp65 and IE-1 proteins or peptides, have been validated in clinical settings. However, it remains unclear to which extend the T-cell response to synthetic peptides reflect that mediated by full-length proteins processed by antigen-presenting cells. We compared the stimulating ability of pp65 and IE-1 proteins and corresponding overlapping peptides in 16 HSCT recip…

IL-17 controls central nervous system autoimmunity through the intestinal microbiome

2021

Interleukin-17A- (IL-17A) and IL-17F-producing CD4(+) T helper cells (T(H)17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). T-H 17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, T-H 17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which…

Prevention of endpoints in primary biliary cholangitis with ursodeoxycholic acid: quantifying the benefit

2020

Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with an established benefit for patients suffering from primary biliary cholangitis (PBC). It was first introduced in the 60s and took until the late 90s to demonstrate a survival benefit in large meta-cohort studies.1 Since then, UDCA is the established first-line therapy according to current guidelines.2 The benefit of UDCA is multidimensional, and patients receiving UDCA experience increased transplant-free survival, a decreased risk of hepatocellular carcinoma and potentially improved quality of life.3–5 The survival benefit is predicted by a number biochemical markers that reflect cholestasis and that are accepted surrogates of the…

Efficacy and Safety of a Preemptive Antiviral Therapy Strategy Based on Combined Virological and Immunological Monitoring for Active Cytomegalovirus …

2016

Preemptive antiviral therapy for active CMV infection in allogeneic stem cell transplant recipients guided by immunological and virological parameters minimizes the risk of recurrent viremia in a subset of patients.

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…