Optimization of an O-balanced bioartificial pancreas for type 1 diabetes using statistical design of experiment.

A bioartificial pancreas (BAP) encapsulating high pancreatic islets concentration is a promising alternative for type 1 diabetes therapy. However, the main limitation of this approach is O supply, especially until graft neovascularization. Here, we described a methodology to design an optimal O-balanced BAP using statistical design of experiment (DoE).

[Extracellular vesicles are players of the immune continuum].

Regulation of immune responses was among the first functions of extracellular vesicles to be identified, more than twenty years ago. What exactly defines the outcome of an immune response remains a challenging issue. Owing to their reduced size, extracellular vesicles easily diffuse in interstitial and lymphatic fluids, where they can interact with the multiple effectors of the immune system.

Molecular and Functional Diversity of Distinct Subpopulations of the Stressed Insulin-Secreting Cell's Vesiculome.

Beta cell failure and apoptosis following islet inflammation have been associated with autoimmune type 1 diabetes pathogenesis. As conveyors of biological active material, extracellular vesicles (EV) act as mediators in communication with immune effectors fostering the idea that EV from inflamed beta cells may contribute to autoimmunity. Evidence accumulates that beta exosomes promote diabetogenic responses, but relative contributions of larger vesicles as well as variations in the composition of the beta cell's vesiculome due to environmental changes have not been explored yet.

Extracellular hemoglobin combined with an O -generating material overcomes O limitation in the bioartificial pancreas.

The bioartificial pancreas encapsulating pancreatic islets in immunoprotective hydrogel is a promising therapy for Type 1 diabetes. As pancreatic islets are highly metabolically active and exquisitely sensitive to hypoxia, maintaining O supply after transplantation remains a major challenge. In this study, we address the O limitation by combining silicone-encapsulated CaO (silicone-CaO ) to generate O with an extracellular hemoglobin O -carrier coencapsulated with islets.

Neu5Gc and α1-3 GAL Xenoantigen Knockout Does Not Affect Glycemia Homeostasis and Insulin Secretion in Pigs.

Xenocell therapy from neonate or adult pig pancreatic islets is one of the most promising alternatives to allograft in type 1 diabetes for addressing organ shortage. In humans, however, natural and elicited antibodies specific for pig xenoantigens, α-(1,3)-galactose (GAL) and -glycolylneuraminic acid (Neu5Gc), are likely to significantly contribute to xenoislet rejection. We obtained double-knockout (DKO) pigs lacking GAL and Neu5Gc.

Trehalose prevents aggregation of exosomes and cryodamage.

Exosomes are important mediators in intercellular communication. Released by many cell types, they transport proteins, lipids, and nucleic acids to distant recipient cells and contribute to important physiopathological processes. Standard current exosome isolation methods based on differential centrifugation protocols tend to induce aggregation of particles in highly concentrated suspensions and freezing of exosomes can induce damage and inconsistent biological activity.

MicroRNA-29b modulates innate and antigen-specific immune responses in mouse models of autoimmunity.

In addition to important regulatory roles in gene expression through RNA interference, it has recently been shown that microRNAs display immune stimulatory effects through direct interaction with receptors of innate immunity of the Toll-like receptor family, aggravating neuronal damage and tumour growth. Yet no evidence exists on consequences of microRNA immune stimulatory actions in the context of an autoimmune disease. Using microRNA analogues, we here show that pancreatic beta cell-derived microRNA sequences induce pro-inflammatory (TNFa, IFNa, IL-12, IL-6) or suppressive (IL-10) cytokine secretion by primary mouse dendritic cells in a sequence-dependent manner.

Pdx-1 or Pdx-1-VP16 protein transduction induces beta-cell gene expression in liver-stem WB cells.

Background: Pancreatic duodenal homeobox-1 (Pdx-1) or Pdx-1-VP16 gene transfer has been shown to induce in vitro rat liver-stem WB cell conversion into pancreatic endocrine precursor cells. High glucose conditions were necessary for further differentiation into functional insulin-producing cells. Pdx-1 has the ability to permeate different cell types due to an inherent protein transduction domain (PTD).

Bipotential mouse embryonic liver (BMEL) cells spontaneously express Pdx1 and Ngn3 but do not undergo further pancreatic differentiation upon Hes1 down-regulation.

Background: Liver-to-pancreas conversion offers new possibilities for beta-cell engineering for type 1 diabetes therapy. Among conceivable sources of liver cells, we focused on BMEL cells. These untransformed mouse embryonic liver cells have been reproducibly isolated from different inbred mice strains and have the potential to differentiate into hepatocytes and cholangiocytes in vitro and in vivo.