Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply.

Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO to a supraphysiological level that maintains all islets viable and functional.

T Induces Both Markers of Maturation and Aging in Pancreatic β-Cells.

Previously, we showed that thyroid hormone (TH) triiodothyronine (T) enhanced β-cell functional maturation through induction of High levels of T have been linked to decreased life span in mammals and low levels to lengthened life span, suggesting a relationship between TH and aging. Here, we show that T increased (a β-cell senescence marker and effector) mRNA in rodent and human β-cells. The kinetics of and induction suggested both genes as targets of TH via TH receptors (THRs) binding to specific response elements.

MAFA and T3 Drive Maturation of Both Fetal Human Islets and Insulin-Producing Cells Differentiated From hESC.

Context: Human embryonic stem cells (hESCs) differentiated toward β-cells and fetal human pancreatic islet cells resemble each other transcriptionally and are characterized by immaturity with a lack of glucose responsiveness, low levels of insulin content, and impaired proinsulin-to-insulin processing. However, their response to stimuli that promote functionality have not been compared.

Objective: The objective of the study was to evaluate the effects of our previous strategies for functional maturation developed in rodents in these two human models of β-cell immaturity and compare their responses.