A5063227663- Pancreatic function and diabetes
- Diabetes and associated disorders
- Cannabis and Cannabinoid Research
- Immune Cell Function and Interaction
- Neuroendocrine Tumor Research Advances
- Diabetes Management and Research
- Renal Transplantation Outcomes and Treatments
- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Genetics and Neurodevelopmental Disorders
- Immune cells in cancer
- Liver Disease Diagnosis and Treatment
- Xenotransplantation and immune response
- Tissue Engineering and Regenerative Medicine
- Long-Term Effects of COVID-19
- Congenital heart defects research
- Organ Transplantation Techniques and Outcomes
- SARS-CoV-2 detection and testing
- Pancreatitis Pathology and Treatment
- Metabolism, Diabetes, and Cancer
- Chemokine receptors and signaling
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Pluripotent Stem Cells Research
IRCCS Ospedale San Raffaele
2013-2024
Vita-Salute San Raffaele University
2012-2021
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2014-2018
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2018
San Raffaele University of Rome
2012-2013
Diabetes Foundation
2013
Plasticity is a hallmark of macrophages, and in response to environmental signals these cells undergo different forms polarized activation, the extremes which are called classic (M1) alternative (M2). Rapamycin (RAPA) crucial for survival functions myeloid phagocytes, but its effects on macrophage polarization not yet studied. To address this issue, human macrophages obtained from six normal blood donors were M1 or M2 vitro by lipopolysaccharide plus interferon-γ interleukin-4 (IL-4),...
Although long considered a promising treatment option for type 1 diabetes, pancreatic islet cell transformation has been hindered by immune system rejection of engrafted tissue. The identification pathways that regulate post-transplant detrimental inflammatory events would improve management and outcome transplanted patients. Here, we found CXCR1/2 chemokine receptors their ligands are crucial negative determinants survival after transplantation. Pancreatic islets released abundant (CXCL1...
The liver is the current site of choice for pancreatic islet transplantation, even though it far from being ideal. We recently have shown in mice that bone marrow (BM) may be a valid alternative to liver, and here we report pilot study test feasibility safety BM as transplantation humans. Four patients who developed diabetes after total pancreatectomy were candidates autologous islet. Because had contraindications intraportal infusion, islets infused BM. In all recipients, engrafted...
Chemokines and their receptors have been associated with or implicated in the pathogenesis of type 1 diabetes (T1D), but identification a single specific chemokine/receptor pathway that may constitute suitable target for development therapeutic interventions is still lacking. Here, we used multiple low-dose (MLD) streptozotocin (STZ) injections NOD mouse model to investigate potency CXCR1/2 inhibition prevent inflammation- autoimmunity-mediated damage pancreatic islets. Reparixin ladarixin,...
Stem memory T cells (Tscm) constitute the earliest developmental stage of cells, displaying stem cell–like properties, such as self-renewal capacity. Their superior immune reconstitution potential has sparked interest in cancer therapy, vaccine development, and reconstitution, whereas their role autoimmunity is largely unexplored. Here we show that autoreactive CD8+ Tscm specific for β-cell antigens GAD65, insulin, IGRP are present patients with type 1 diabetes (T1D). In vitro, generation...
Biobanks are imperative infrastructures, particularly during outbreaks, when there is an obligation to acquire and share knowledge as quick possible allow for implementation of science-based preventive, diagnostic, prognostic, therapeutic strategies.We established a COVID-19 biobank with the aim collecting high-quality well-annotated human biospecimens, in effort understand pathogenic mechanisms underlying identify targets (COVID-BioB, NCT04318366). Here we describe our experience briefly...
High levels of donor-derived CCL2 have been associated with poor islet allograft outcome in patients type 1 diabetes. The aim our work was to determine whether secreted by the has independent proinflammatory effects that influence engraftment and graft acceptance. Both mice humans is significantly positively other cytokines/chemokines, particular highly released “proinflammatory” IL-6 CXCL8 or CXCL1. Transplantation CCL2-/- islets into syngenic recipients did not improve transplant function....
Advances in islet transplantation research have led to remarkable improvements the outcome humans with type 1 diabetes. However, pitfalls, mainly linked both early liver-specific inflammatory events and pre-existing transplant-induced auto- allo-specific adaptive immune responses, still remain. In this scenario into pancreatic transplantation, essential investigate new strategies overcome open issues, needs very well-designed preclinical studies obtain consistent reliable results select only...
The aim of this study was to characterize the immune response against intrabone marrow (BM-Tx) or intraliver (liver-Tx) transplanted islets in presence absence immunosuppression.Less (C57BL/6 Balb/c) and highly (Balb/c C57BL/6) stringent major histocompatibility complex fully mismatched mouse models were used evaluate alloimmune response. Single antigen-mismatched model RIP-GP antigen-specific Mice received tacrolimus (FK-506, 0.1 mg/kg per day)/mycophenolate mofetil (MMF, 60 day), anti-CD3...
In Brief Background The identification of pathway(s) playing a pivotal role in peritransplant detrimental inflammatory events represents the crucial step toward better management and outcome pancreatic islet transplanted patients. Recently, we selected CXCR1/2 inhibition as relevant strategy enhancing survival after transplantation. Methods Here, most clinically used anti-inflammatory compounds (IL1-receptor antagonist, steroids, TNF-α inhibitor) alone or combination with inhibitor were...
Objective Immunosuppression (IS) in islet transplantation (Tx) is a double-edged sword: it prevents immunoreaction but has the potential to impair engraftment. The aim of this study was identify murine animal models IS platform with best balance between these two opposite effects. Methods To impact on engraftment diabetic C57BL/6 mice were transplanted 350 syngeneic islets through portal vein and treated once-daily either rapamycin (RAPA; 0.1–0.5–1 mg/kg ip), tacrolimus (FK506; mycophenolate...
Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of autotransplantation performed pancreatectomy. To model this risk, islets and/or exocrine clusters obtained from genetically engineered mouse for ductal adenocarcinoma (the LSL-KrasG12D/+ ;LSL-Trp53R172H/+ ;Pdx-1-Cre, termed KPC mouse) were transplanted via the portal vein in syngeneic wild type (WT) severely diabetic recipients following treatment groups: group A (n = 11) received volume equal to 250...
SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity identification early biomarkers capable stratifying patient based risk progression could allow tailored treatments.
In the article listed above, there is an error in Fig. 3. panel B , immunohistochemical staining of insulin ( top middle …
Objective: The aim of our work is to determine whether the CXCR2 inhibition improves islet transplantation outcome. Methods and Results: Liver inflammatory status was studied before after intrahepatic (Tx) 500 syngeneic islets in diabetic C57BL/6 mice. Cytokine chemokine transcripts 4h-24h-48h Tx were determined using RNAse protection assays. Intrahepatic leucocyte (IHL) infiltration 1, 3, 5, 7, 10, 14 days by FACS. mRNA for CXCL1/KC strongly induced immediately infusion (100-fold increase...
Objective: The goal of this study was to evaluate safety and feasibility bone marrow (BM) as site for islet transplantation (Tx) in humans. Our hypothesis is that BM represents a better than liver thanks its potential capacity favor engraftment face more easiness access bioptic follow up. Method: A pilot has been approved by the Italian Regulatory Agencies August 2009 (NCT01345227). We were permitted perform single intra infusion at level iliac crest patients having contraindications...