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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 O2 supply, especially until graft neovascularization. Here, we described a methodology to design an optimal O2-balanced BAP using statistical design of experiment (DoE). A full factorial DoE was first performed to screen two O2-technologies on their ability to preserve pseudo-islet viability and function under hypoxia and normoxia. Then, response surface methodology was used to define the optimal O2-carrier and islet seeding concentrations to maximize the number of viable pseudo-islets in the BAP containing an O2-generator under hypoxia. Monitoring of viability, function and maturation of neonatal pig islets for 15 days in vitro demonstrated the efficiency of the optimal O2-balanced BAP. The findings should allow the design of a more realistic BAP for humans with high islets concentration by maintaining the O2 balance in the device. [ABSTRACT FROM AUTHOR]

Adrenergic receptor agonists and antagonists are extensively used as drugs in medicine for a broad spectrum of indications. We examined the consequences of β2-adrenergic stimulation of murine dendritic cells (DCs) on CD4 T cell activation. We demonstrated in vitro that treatment of LPS-matured DCs with the β2-agonist salbutamol reduced their ability to trigger OT-II T cell proliferation specific for ovalbumin antigen. Salbutamol also induced a decrease in MHC class II molecule expression by DC through Gi protein activation. Co-culture of CD4 T cells with salbutamol-conditioned mature DC impaired TNFα and IL-6 secretion while preserving IL-10 production by T cells. Using a vaccination protocol in mice, we showed that salbutamol favored IL-10-producing CD4 T cells. None of these effects was observed when working with β2-adrenoreceptor deficient mice. Finally, we suggest that β2-adrenergic stimulation of DC could be an interesting way to shape CD4 T cell responses for the purposes of immunotherapy. [ABSTRACT FROM AUTHOR]