Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we studied pancreata from healthy adult donors and investigated a single cell surface adhesion molecule, desmoglein-2 (DSG2).
View Article and Find Full Text PDFObjective: To characterise the clinical phenotypes and genetic variants of hereditary pancreatitis in people diagnosed in South Australia.
Design, Setting, Participants: Cross-sectional study of people who received molecular diagnoses of hereditary pancreatitis from one of four major diagnostic services in South Australia, 1 January 2006 - 30 June 2021.
Main Outcome Measures: Genotypic and clinical features of people with hereditary pancreatitis, including age at onset, attack frequency, pain indices, use of opioid medications, and physical and mental health impact of hereditary pancreatitis.
Background: The initial response to islet transplantation and the subsequent acute inflammation is responsible for significant attrition of islets following both autologous and allogenic procedures. This multicentre study compares this inflammatory response using cytokine profiles and complement activation.
Methods: Inflammatory cytokine and complement pathway activity were examined in two cohorts of patients undergoing total pancreatectomy followed either by autologous (n=11) or allogenic (n=6) islet transplantation.
The field of regenerative medicine provides enormous opportunities for generating beta cells from different stem cell sources for cellular therapy. Even though insulin-secreting cells can be generated from a variety of stem cell types like pluripotent stem cells and embryonic stem cells, the ideal functional cells should be generated from patients' own cells and expanded to considerable levels by non-integrative culture techniques. In terms of the ease of isolation, plasticity, and clinical translation to generate autologous cells, mesenchymal stem cell stands superior.
View Article and Find Full Text PDFPurpose Of Review: Pancreatic islet cell transplantation is currently the only curative cell therapy for type 1 diabetes mellitus. However, its potential to treat many more patients is limited by several challenges. The emergence of 3D bioprinting technology from recent advances in 3D printing, biomaterials, and cell biology has provided the means to overcome these challenges.
View Article and Find Full Text PDFOver the last two decades, pancreatic islet transplantations have become a promising treatment for Type I diabetes. However, although providing a consistent and sustained exogenous insulin supply, there are a number of limitations hindering the widespread application of this approach. These include the lack of sufficient vasculature and allogeneic immune attacks after transplantation, which both contribute to poor cell survival rates.
View Article and Find Full Text PDFPorous silicon nanoparticles (pSiNP), modified to target dendritic cells (DC), provide an alternate strategy for the delivery of immunosuppressive drugs. Here, we aimed to develop a DC-targeting pSiNP displaying c-type lectin, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and CD11c monoclonal antibodies. The in vivo tracking of these fluorescent DC-targeting nanoparticles was assessed in both C57BL/6 mice and common marmosets ( Callithrix jacchus) by intravenous injection (20 mg/kg).
View Article and Find Full Text PDFDendritic cells (DC) are the most potent antigen-presenting cells and are fundamental for the establishment of transplant tolerance. The Dendritic Cell-Specific Intracellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN; CD209) receptor provides a target for dendritic cell therapy. Biodegradable and high-surface area porous silicon (pSi) nanoparticles displaying anti-DC-SIGN antibodies and loaded with the immunosuppressant rapamycin (Sirolimus) serve as a fit-for-purpose platform to target and modify DC.
View Article and Find Full Text PDFPancreatic islet transplantation has become a recognized therapy for insulin-dependent diabetes mellitus. During isolation from pancreatic tissue, the islet microenvironment is disrupted. The extracellular matrix (ECM) within this space not only provides structural support, but also actively signals to regulate islet survival and function.
View Article and Find Full Text PDFThe success of pancreatic islet transplantation is limited by delayed engraftment and suboptimal function in the longer term. Endothelial progenitor cells (EPCs) represent a potential cellular therapy that may improve the engraftment of transplanted pancreatic islets. In addition, EPCs may directly affect the function of pancreatic β-cells.
View Article and Find Full Text PDFPancreatic islet transplantation is limited by extensive apoptosis and suboptimal function of the implanted islets in the longer term. Endothelial progenitor cells (EPC) may be ideal for enhancing both the survival and function of transplanted islets. Here, we describe for the first time the in vitro formation of rat mosaic pseudoislets comprised of pancreatic β-cells with interspersed vasculogenic EPC.
View Article and Find Full Text PDFPhenoxodiol (2H-1-benzopyran-7-0,1, 3-[4-hydroxyphenyl], PXD) is a synthetic analogue of the naturally-occurring plant isoflavone and anticancer agent, genistein. PXD directly induces mitotic arrest and apoptosis in most cancer cells and is currently undergoing clinical trials, as a chemotherapeutic in ovarian and prostate cancers. We show here that PXD also exhibits potent antiangiogenic properties.
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