Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Islet transplantation and more recently stem cell-derived islets were shown to successfully re-establish glycemic control in people with type 1 diabetes under immunosuppression. These results were achieved through intraportal infusion which leads to early graft losses and limits the capacity to contain and retrieve implanted cells in case of adverse events. Extra-hepatic sites and encapsulation devices have been developed to address these challenges and potentially create an immunoprotective or immune-privileged environment. Many strategies have achieved reversal of hyperglycemia in diabetic rodents. So far, the results have been less promising when transitioning to humans and larger animal models due to challenges in oxygenation and insulin delivery. We propose a versatile in vitro perfusion system to culture and experimentally study the function of centimeter-scale tissues and devices for insulin-secreting cell delivery. The system accommodates various tissue geometries, experimental readouts, and oxygenation tensions reflective of potential transplantation sites. We highlight the system's applications by using case studies to explore three prominent bioartificial endocrine pancreas (BAP) configurations: (I) with internal flow, (II) with internal flow and microvascularized, and (III) without internal flow. Oxygen concentration profiles modeled computationally were analogous t

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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