Can a Spoonful of Sugar Help the Beta Cells Hang ‘Round?
What do you get when you put 57 surgeons, immunologists, cell biologists, and engineers together in one room? The JDRF Encapsulation Consortium; a cross-disciplinary team of academic and industry researchers who work collaboratively to advance beta cell replacement therapies for type 1 diabetes (T1D). Beta cell replacement involves implanting functional insulin-producing pancreatic beta cells into people whose own beta cells have been destroyed by autoimmune attacks and protecting the cells—without the use of immune suppressing drugs—so they can produce insulin. Early versions of the therapy could ease the threat of extreme blood-sugar swings, and more advanced versions could one day enable insulin independence.
A recent two-day meeting of the Consortium discussed dozens of intriguing projects advancing beta cell replacement technologies.
A presentation from McGill University chemical engineering professor Corinne Hoesli, Ph.D., who used sugar and a 3D printer to create an encapsulation device to enhance the survival and performance of implanted beta cells. Dr. Hoesli has molded an implant shot through with channels to encourage the growth of capillaries that will nourish and provide oxygen to the beta cells inside. She uses a 3D printer and a sugar-based “carbohydrate glass” to create a mold that can be filled with a gel containing beads full of cells that are protected by a coating made from algae. When the sugar is melted away, blood flow can be circulated through the device to nourish the cells and keep them alive and functioning. The next step is to use the device filled first with mouse cells and then with human beta cell precursors to see whether the cells can survive, mature and produce insulin when implanted into mice.
An update from Mark Poznansky, M.D., Ph.D., on CXCL12, a naturally-occurring protein that repels destructive immune cells that damage or destroy implanted beta cells. He and his team have already demonstrated that coating cells with a protective algae-based shell that includes CXCL12 successfully protects pig islets from immune attack when transplanted into diabetic mice and even reverses their diabetes, all without the use of immunosuppressive drugs. Now they’re looking at whether the protein is equally effective at protecting human stem cell-derived beta cells produced in the lab of Harvard colleague Doug Melton, Ph.D.
Australian transplant immunologist Shane Grey, Ph.D., says he’s found a way to make implanted islet cells protect themselves from autoimmune attacks. His team at the Garvan Institute of Medical Research has demonstrated that forcing beta cells to express the A20 protein protected islets transplanted between two different types of mice from immune attack and improved their function. According to Dr. Grey, A20 is one of the most important regulators of cell inflammation, acting to calm inflammatory pathways within the cells themselves. A20 also attracts T regulatory (Treg) cells that combat the autoimmune reaction while suppressing formation of T effector cells (Teffs) implicated in autoimmunity. Dr. Grey refers to A20 as “cellular armor” that could help islets survive the implant process, which currently kills about half of them within a week of the procedure. In his current project, Dr. Grey is transplanting pig islets expressing A20 into humanized mice to assess their survival and ability to control blood glucose.
JDRF Director of Translational Development Esther Latres, Ph.D., says the Consortium’s ability to find and fund such innovative investigators is crucial to driving progress in beta cell replacement. “Research developments from the Consortium look very promising,” she says, “and one key element of success is incorporating new technology approaches, cell delivery systems, or sources of insulin-producing cells from our newly funded investigators.”