Bioartifical Pancreas for Transplanted Human Islet Cells for T1DM

A bioartificial pancreas for transplanted islet cells which does not affect the immune system could reduce the need for chronic immunosupression to prevent rejection…. 

Researchers have developed an "oxygenated chamber system composed of immune-isolating alginate and polymembrane covers that allows for survival and function of islets cells without immunosuppression." The goal was to see if this method could survive over an extended follow up period of 10 months without immunosupression or complications, and still be glucose responsive. Practicality of the device and the oxygen refill procedures were also evaluated.

One 63 year old man with a long history of type 1 diabetes with complete insulin deficiency and average glucose control was transplanted. The device was placed without complications. Pain was limited to a couple days, and there wasn’t any discomfort associated with the inserted chamber. Oxygen supply in the gas reservoir was replenished daily by the patient himself. Graft function was assessed by using blood glucose measurements, stimulated C-peptide, and local stimulation of hormone release from the implanted islet chamber. Graft function was persistent throughout the 10 month period. The basal hormone and C-peptide level were low but still provided successful graft function. A high-glucose test was given and rapid insulin secretion was observed showing that the islet is responsive to increased glucose levels. There was no change in islet autoantibody or donor alloantibody.

The idea of islet macroencapsulation has been successful in animal trials, and now with this study it has shown promising results for human trials. The goal of the study was accomplished. No immunosuppressives were used and there was still no graft rejection noted. The islets were functional throughout the entire period but only moderate improvements in diabetes care were seen. HbA1c levels were moderately improved and insulin requirements were reduced. The low basal C-peptide level maintained could be explained by the small mass of islet cells transplanted. Only 2,100 cells per kg were implanted compared to 5,000 or even 10,000 suggested by other studies. Two areas for improvement might include preconditioning islet cells with new agonists of growth hormone-releasing hormone, or using cells from other animal species. Still, this research has opened the door for a new type of therapy. "The chamber system has the potential to evolve into a successful and safe approach for clinical application of cell based-therapies, including cells from xenogeneic sources."

Ludwig, B. et al. Transplantation of Human Islets Without Immunosupression. PNAS 2013: 13175611v1-201317561.