The generation of functional human islet-like organoids (HILOs) that can restore glucose homeostasis without immune rejection after transplantation into diabetic mice is reported in Nature this week.
The transplantation of islets — clusters of hormone-producing cells of the pancreas — provides a method for long-term glucose control in people with type 1 and late-stage type 2 diabetes, but islets sourced from cadavers vary in quality and are limited in availability. Insulin-producing pancreatic beta cells derived from human stem cells could also provide long-term relief from insulin-dependent diabetes or transplantation, but generating functional beta cells has remained challenging.
Ronald Evans and colleagues report a technique for generating three-dimensional HILOs that could represent an alternative source of transplantable endocrine-like cells that can restore long-term glycaemic control without the need for chronic immunosuppression. The authors exploit the Wnt signalling pathway to facilitate the metabolic maturation of the HILOs necessary for insulin secretion, and their method induces expression of the PD-L1 immune checkpoint protein and prevents immune rejection for 50 days after transplantation into diabetic mice.
The study contributes to ongoing efforts to develop alternative therapies to treat diabetes that do not rely on cadaveric sources, which require immune suppression, or device-dependent technologies.
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