Long-term cultures of human pancreatic islets in self-assembling peptides hydrogels.

Human pancreatic islets transplantation is an experimental therapeutic treatment for Type I Diabetes. Limited islets lifespan in culture remains the main drawback, due to the absence of native extracellular matrix as mechanical support after their enzymatic and mechanical isolation procedure. Extending the limited islets lifespan by creating a long-term culture remains a challenge.

Human skin processing affects clinical outcome in allograft recipients.

Skin allografts represent a milestone in burn patient treatment. However, skin procurement is still burdened by high rates of contamination, and validation procedures have not yet been standardized. In addition, it is not clear if tissue viability affects allograft skin outcomes.

The IGFBP3/TMEM219 pathway regulates beta cell homeostasis.

Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis.

Heterogeneity of Human Pancreatic Islet Isolation Around Europe: Results of a Survey Study.

Background: Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes, and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries.

Methods: A web-based questionnaire about critical steps, including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation, and release criteria of the product, was completed by isolation facilities participating at the Ninth International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan.

Human Engineered Cartilage and Decellularized Matrix as an Alternative to Animal Osteoarthritis Model.

(1) Objective: to obtain a reproducible, robust, well-defined, and cost-affordable in vitro model of human cartilage degeneration, suitable for drug screening; (2) Methods: we proposed 3D models of engineered cartilage, considering two human chondrocyte sources (articular/nasal) and five culture methods (pellet, alginate beads, silk/alginate microcarriers, and decellularized cartilage). Engineered cartilages were treated with pro-inflammatory cytokine IL-1β to promote cartilage degradation; (3) Results: articular chondrocytes have been rejected since they exhibit low cellular doubling with respect to nasal cells, with longer culture time for cell expansion; furthermore, pellet and alginate bead cultures lead to insufficient cartilage matrix production. Decellularized cartilage resulted as good support for degeneration model, but long culture time and high cell amount are required to obtain the adequate scaffold colonization.

Long-term Effect of Islet Transplantation on Glycemic Variability.

Islet transplantation has been reported to restore normoglycemia and the overall metabolic control in type 1 diabetes mellitus (DM). In the most experienced centers, islet transplantation clinical outcome is similar to that of the whole pancreas transplantation. Long-term islet transplantation function remains a very interesting matter worth discussing.

Islet transplantation 30 years after the first transplants.

First clinical islet allotransplantation in patients affected by type 1 diabetes mellitus was performed about 30 years ago. Despite the progressive improvement of the success rate, the clinical indication to the islet allotransplantation remains limited to selected patients affected by brittle type 1 diabetes mellitus. The burden of the immunosuppression therapy still represents the main critical issue but other areas might be subject to further improvements, such as the islet production, islet engraftment and long-term function.

Stromal Vascular Fraction Loaded Silk Fibroin Mats Effectively Support the Survival of Diabetic Mice after Pancreatic Islet Transplantation.

The aim of this study is to assess whether stromal vascular fraction (SVF)-soaked silk fibroin nonwoven mats (silk-SVF) can preserve the functionality of encapsulated pancreatic endocrine cells (alginate-PECs) after transplantation in the subcutaneous tissue of diabetic mice. Silk scaffolds are selected to create an effective 3D microenvironment for SVF delivery in the subcutaneous tissue before diabetes induction: silk-SVF is subcutaneously implanted in the dorsal area of five healthy animals; after 15 d, mice are treated with streptozotocin to induce diabetes and then alginate-PECs are implanted on the silk-SVF. All animals appear in good health, increasing weight during time, and among them, one presents euglycemia until the end of experiments.

Islet Transplantation in Pediatric Patients: Current Indications and Future Perspectives.

The first islet transplantation in diabetes mellitus was performed more than 20 years ago. Since then, clinical results have progressively improved. Nowadays, islet transplantation can be considered a real therapeutic option after pancreatectomy for painful chronic pancreatitis (autotransplantation) and in selected adult patients affected by type 1 diabetes mellitus (allotransplantation).

Mesenchymal stromal cells loading curcumin-INVITE-micelles: a drug delivery system for neurodegenerative diseases.

This work reports on the formation of a carrier-in-carrier device for the systemic delivery and targeting of hydrophobic drugs mediated by micelle-loaded mesenchymal stromal cells (MSCs) (carrier-in-carrier) to be administered by intravenous injection. The innate ability of MSCs to reach injured tissues such as the central nervous system or other damaged tissues, is the key for the second order delivery and first order targeting. Inulin-D-alfa-tocopherol succinate micelles (INVITE M) are able to incorporate highly hydrophobic drugs and, due to their dimensions (≈7 nm diameter), to penetrate the cell membrane easily and quickly.

Formulation and characterization of silk fibroin films as a scaffold for adipose-derived stem cells in skin tissue engineering.

Skin substitutes are epidermal, dermal or complete bilayered constructs, composed by natural or synthetic scaffolds and by adherent cells such as fibroblasts, keratinocytes or mesenchymal stem cells. Silk fibroin is a promising polymer to realize scaffolds, since it is biocompatible, biodegradable, and exhibits excellent mechanical properties in terms of tensile strength. Moreover, fibroin can be added of others components in order to modify the biomaterial properties for the purpose.

GMP-compliant culture of human hair follicle cells for encapsulation and transplantation.

Human hair follicle cells, both bulge and dermal papilla cells, were isolated and cultured in a GMP cell factory, in order to obtain an in vitro hair follicle source for encapsulation end transplantation in alopecia regenerative cell therapy. An in vitro model, constituted by organotypic cultures of human skin sample, was set up to simulate the dermal-epidermal interaction between bulge cells and dermal papilla cells, evaluating the possible new follicles formation and the regenerative potentiality of these hair follicle cells. Both the bulge and dermal papilla cells show an excellent cellular proliferation as well as an abundant extracellular matrix production.

Regenerated silk fibroin scaffold and infrapatellar adipose stromal vascular fraction as feeder-layer: a new product for cartilage advanced therapy.

Articular cartilage has limited repair and regeneration potential, and the scarcity of treatment modalities has motivated attempts to engineer cartilage tissue constructs. The use of chondrocytes in cartilage tissue engineering has been restricted by the limited availability of these cells, their intrinsic tendency to lose their phenotype during the expansion, as well as the difficulties during the first cell adhesion to the scaffold. Aim of this work was to evaluate the intra-articular adipose stromal vascular fraction attachment on silk fibroin scaffold to promote chondrocytes adhesion and proliferation.

Co-graft of allogeneic immune regulatory neural stem cells (NPC) and pancreatic islets mediates tolerance, while inducing NPC-derived tumors in mice.

Background: Data available on the immunomodulatory properties of neural stem/precursor cells (NPC) support their possible use as modulators for immune-mediated process. The aim of this study was to define whether NPC administered in combination with pancreatic islets prevents rejection in a fully mismatched allograft model.

Methodology/principal Finding: Diabetic Balb/c mice were co-transplanted under the kidney capsule with pancreatic islets and GFP(+) NPC from fully mismatched C57BL/6 mice.

Interaction of an extended series of N-substituted di(2-picolyl)amine derivatives with copper(II). Synthetic, structural, magnetic and solution studies.

The interaction of Cu(II) with the following secondary N-substituted derivatives of di(2-picolyl)amine () are reported: N-cyclohexylmethyl-di(2-picolyl)amine (), N-benzyl-di(2-picolyl)amine (), N-(4-pyridylmethyl)-di(2-picolyl)amine (), N-(4-carboxymethylbenzyl)-di(2-picolyl)amine (), N-(9-anthracen-8-ylmethyl)-di(2-picolyl)amine (), 1,3-bis[di(2-picolyl)aminomethyl]benzene (), 1,4-bis[di(2-picolyl)aminomethyl]benzene () and 2,4,6-tris[di(2-picolyl)amino]triazine (). The solid complexes [Cu()(micro-Cl)](2)(PF(6))(2), [Cu()(micro-Cl)](2)(PF(6))(2).0.

Collagenase isoforms for pancreas digestion.

The available information concerning the characteristics and composition of collagenase batches, which are effective in the digestion of human pancreas for islet transplants, is scarce and incomplete. A large inter- and intrabatched variability in activity and efficiency of blend enzymes available for isolation has been observed. The aim of this study was to characterize enzyme blend components.

Abscisic acid is an endogenous stimulator of insulin release from human pancreatic islets with cyclic ADP ribose as second messenger.

Abscisic acid (ABA) is a plant stress hormone recently identified as an endogenous pro-inflammatory cytokine in human granulocytes. Because paracrine signaling between pancreatic beta cells and inflammatory cells is increasingly recognized as a pathogenetic mechanism in the metabolic syndrome and type II diabetes, we investigated the effect of ABA on insulin secretion. Nanomolar ABA increases glucose-stimulated insulin secretion from RIN-m and INS-1 cells and from murine and human pancreatic islets.

Assembly of a trinuclear metallo-capsule from a tripodal tris(beta-diketone) derivative and copper(II).

A new metallo-capsule has been synthesised that consists of three copper(II) ions and two molecules of a tris-deprotonated tripodal ligand in which three 2,4-pentanedione groups are linked via their gamma-carbons through thioether spacers to the 1,3,5-positions of a triazine core.

Prolonged islet allograft survival in diabetic mice upon macrophage depletion by clodronate-loaded erythrocytes.

Early impairment of islet function and graft loss strongly limit the success of allogenic islet transplantation in insulin-dependent diabetes. Macrophages play a key role in this process thus the depletion of these cells may strongly affect islet survival. In this study, we have evaluated the effect of the depletion of macrophages in mouse allograft rejection using a new approach based on a single infusion of red blood cells loaded with the synthetic analogue of pyrophosphate clodronate.

Characterization of collagenase blend enzymes for human islet transplantation.

Background: Efficient islet isolation represents a necessary requirement for successful islet transplantation as a treatment for type 1 diabetes. The choice of collagenase for pancreas digestion is critical for the isolation outcome, and Liberase is the most widely used enzyme, although large intra-batched variability in activity and efficiency has been observed.

Methods: The aim of this study was to characterize Liberase components and their relative role in pancreas digestion.

Silver(I) complexation of linked 2,2'-dipyridylamine derivatives. Synthetic, solvent extraction, membrane transport and X-ray structural studies.

Synthesis of the 2,2'-dipyridylamine derivatives di-2-pyridylaminomethylbenzene 1, 1,2-bis(di-2-pyridylaminomethyl)benzene 2, 1,3-bis(di-2-pyridylaminomethyl)benzene 3, 2,6-bis(di-2-pyridylaminomethyl)pyridine 4, 1,4-bis(di-2-pyridylaminomethyl)benzene 5, and 1,3,5-tris(di-2-pyridylaminomethyl)benzene 6 are reported together with the single-crystal X-ray structures of 2, 3, and 5. Reaction of individual salts of the type AgX (where X = NO(3)(-), PF(6)(-), ClO(4)(-), or BF(4)(-)) with the above ligands has led to the isolation of thirteen Ag(I) complexes, nine of which have also been characterised by X-ray diffraction. In part, the inherent flexibility of the respective ligands has resulted in the adoption of a range of coordination arrangements.

Culture medium modulates proinflammatory conditions of human pancreatic islets before transplantation.

A portion of transplanted islets is lost during engraftment as a result of stressful events, involving hypoxia and production of proinflammatory molecules by islets. Two of these molecules (monocyte chemoattractant protein-1, CCL2/MCP-1 and tissue factor, TF) are directly correlated with reduced graft function. We evaluated which factors reduce islet proinflammatory conditions.

Assembly of a tri-silver metallo-capsule incorporating a tripodal tris-pyridyl ligand.

A trinuclear metallo-capsule has been assembled from a new tripodal pyridyl ligand and three silver(I) ions; the X-ray structure shows the presence of a Ag-Ag interaction in the solid state giving rise to a non-symmetric capsule arrangement while NMR evidence indicates that the structure in solution is symmetrical.