A5038917516- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Immune Cell Function and Interaction
- Cannabis and Cannabinoid Research
- Hematopoietic Stem Cell Transplantation
- Mesenchymal stem cell research
- Renal Transplantation Outcomes and Treatments
- Organ Transplantation Techniques and Outcomes
- T-cell and B-cell Immunology
- Diabetes Treatment and Management
- Hematological disorders and diagnostics
- Xenotransplantation and immune response
- Pluripotent Stem Cells Research
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Immunotherapy and Immune Responses
- Bone and Joint Diseases
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Organ and Tissue Transplantation Research
- Liver physiology and pathology
- Congenital Diaphragmatic Hernia Studies
- Medical Imaging and Analysis
- Chromosomal and Genetic Variations
University of Miami
2014-2024
Miami Transplant Institute
1997-2021
Benaroya Research Institute
2018
University of Illinois Urbana-Champaign
2014
Bipar
2008
Dr V Seshiah Diabetes Research Institute
2005
Beth Israel Deaconess Medical Center
2004
Boston University
2004
Massachusetts General Hospital
2004
Joslin Diabetes Center
2004
The cytoarchitecture of human islets has been examined, focusing on cellular associations that provide the anatomical framework for paracrine interactions. By using confocal microscopy and multiple immunofluorescence, we found that, contrary to descriptions prototypical in textbooks literature, did not show subdivisions. Insulin-immunoreactive β cells, glucagon-immunoreactive α somatostatin-containing δ cells were scattered throughout islet. Human clustered, most (71%) showed with other...
Reported effects of anti-CD154 treatment on autoimmunity, alloreactivity, and inflammatory events mediated by macrophages endothelial cells indicated that it might be an ideal agent for the prevention intrahepatic islet allograft failure. This hypothesis was tested in MHC-mismatched rhesus monkeys. Transplantation adequate number viable islets resulted engraftment insulin independence six recipients treated with (hu5c8) induction plus monthly maintenance therapy (post-operative day >125,...
Following the success obtained with transplantation of fresh human islets under steroid-free immunosuppression, this trial evaluated that had undergone a period in vitro culture and potential tumor necrosis factor (TNF-alpha) blockade to improve islet engraftment. Subjects included 16 patients type 1 diabetes mellitus (T1DM); half were randomly assigned receive Infliximab immediately preceding initial infusion. Immunosuppression consisted daclizumab induction sirolimus/tacrolimus...
Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects could yield beneficial ARDS. The objective of this study was determine safety explore efficacy umbilical cord mesenchymal cell (UC-MSC) infusions subjects A double-blind, phase 1/2a, randomized, controlled trial performed. Randomization stratification by ARDS severity used foster balance among groups. All were...
Clinical islet cell transplantation has resulted in insulin independence a limited number of cases. Rejection, recurrence autoimmunity, and impairment normal function by conventional immunosuppressive drugs, e.g., steroids, tacrolimus, cyclosporin A, may all contribute to allograft loss. Furthermore, intraportal infusion allogeneic islets results the activation intrahepatic macrophages endothelial cells, followed production proinflammatory mediators that can primary nonfunction. We reasoned...
OBJECTIVE To test the graft-promoting effects of mesenchymal stem cells (MSCs) in a cynomolgus monkey model islet/bone marrow transplantation. RESEARCH DESIGN AND METHODS Cynomolgus MSCs were obtained from iliac crest aspirate and characterized through passage 11 for phenotype, gene expression, differentiation potential, karyotype. Allogeneic donor cotransplanted intraportally with islets on postoperative day (POD) 0 intravenously PODs 5 11. Recipients followed stabilization blood glucose...
Abstract In recent years, reagents have been developed that specifically target signals critical for effective T cell activation and function. Manipulation of the CD28/CD80/86 CD40/CD154 pathways has exhibited extraordinary efficacy, particularly when are blocked simultaneously. Despite reported efficacy anti-CD154 in rodents higher models, its future clinical use is uncertain due to thromboembolic events trials. To circumvent this potential complication, we evaluated a chimeric Ab targeting...
The aim of this study was to test whether an omental pouch can be used as alternative site for islet implantation in diabetic monkeys. Here we report the successful engraftment islets cynomolgus monkeys when loaded on a synthetic biodegradable scaffold and placed pouch. One autologous five allogeneic monkey transplants under cover steroid-free immune suppression (SFIS) were undertaken. Fasting blood glucose (FBG) C-peptide (CP), exogenous insulin requirements (EIR), intravenous tolerance...
OBJECTIVE A pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized 1) ATG/GCSF or 2) ATG alone would slow the decline of β-cell function patients new-onset T1D <100 days). RESEARCH DESIGN AND METHODS three-arm, randomized, double-masked, placebo-controlled trial was performed by Type...
OBJECTIVE We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS studied 1,244 TrialNet Pathway Prevention study participants (T1D patients’ relatives without with one or more positive autoantibodies) who were genotyped Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up...
Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role plays human islets. We now show the presence of an signaling pathway that enhances β cell's sensitivity and responsiveness to glucose fluctuations. By using situ hybridization, RT-PCR, immunohistochemistry, Western blotting well recordings cytoplasmic-free Ca 2+ concentration, [Ca ] i , hormone release vitro, we cells express ionotropic receptors P2X 3 type activation these by coreleased...
Transplantation of pancreatic islets is a therapeutic option to preserve or restore β-cell function. Our study was aimed at developing clinically applicable protocol for extrahepatic transplantation islets. The potency implanted onto the omentum, using an in situ–generated adherent, resorbable plasma-thrombin biologic scaffold, evaluated diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment scaffold confirmed by achievement improved metabolic function preservation...
Clinical islet transplantation has demonstrated success in treating type 1 diabetes. A current limitation is the intrahepatic portal vein transplant site, which prone to mechanical stress and inflammation. Transplantation of pancreatic islets into alternative sites preferable, but challenging, as it may require a three-dimensional vehicle confer protection confine well-defined, retrievable space where neovascularization can occur. We have fabricated biostable, macroporous scaffolds from...
Attaining glycemic targets without severe hypoglycemic events (SHEs) is a challenging treatment goal for patients with type 1 diabetes complicated by impaired awareness of hypoglycemia (IAH). The CIT Consortium Protocol 07 (CIT-07) trial showed islet transplantation to be an effective subjects IAH and intractable SHEs. We evaluated health-related quality life (HRQOL), functional health status, utility before after pancreatic in CIT-07 participants.Four surveys, the Diabetes Distress Scale...
Eight type 1 diabetic patients, ages 29–41 years, with mean diabetes duration of 23 years (range 18–29 years) received islet transplants from to 5 donors. Seven patients had stable kidney allografts 1–11 before the transplant, and one patient a simultaneous islet-kidney allograft. Patients' blood glucose control was poor as reflected by ± SD HbA1c 9.1 1.7% transplant. Of first three two (1 3) achieved insulin independence for 36 38 days, respectively. Two recipients rejected their grafts...
Recent success using a steroid-free immunosuppressive regimen has renewed enthusiasm for the use of islet transplantation to treat diabetes. Toxicities associated with continued calcineurin inhibitor may limit wide-spread application this therapy. Biological agents that block key T-cell costimulatory signals, in particular CD28 pathway, have demonstrated extraordinary promise animal models. LEA29Y (BMS-224818), mutant CTLA4-Ig molecule increased binding activity, was evaluated its potential...
Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing Encapsulation (NICHE) device, which integrates direct vascularization facile mass transfer localized immunosuppressant delivery rejection prophylaxis. Here, investigated NICHE allogeneic long-term reversal in an immunocompetent, male rat model. We...
Abstract We recently reported acute COVID-19 symptoms, clinical status, weight loss, multi-organ pathological changes, and animal death in a murine hepatitis virus-1 (MHV-1) coronavirus mouse model of COVID-19, which were similar to that observed humans with COVID-19. further examined long-term (12 months post-infection) sequelae these mice. Congested blood vessels, perivascular cavitation, pericellular halos, vacuolation neuropils, pyknotic nuclei, eosinophilic necrosis, necrotic neurons...