Human Trials with Microencapsulated Insulin-Producing Cells: Past, Present and Future

Author(s): Bernard Tuch, Vijayaganapathy Vaithilingam and Jayne Foster

Pp: 40-69 (30)

* (Excluding Mailing and Handling)

Abstract

Microencapsulation of insulin-producing cells is a promising strategy to deliver a cell therapy for treatment of type 1 diabetes without the need for anti-rejection drugs. In this Chapter, we describe our experience in producing microcapsules made of barium alginate, and their application pre-clinically in diabetic rodents and pigs before moving to the clinic in a first-in-man trial with encapsulated human islets. Whilst the use of the microcapsules was safe in the clinical trial, we have learnt from the trial that it is necessary to modify the microcapsule to reduce pericapsular fibrosis, and strategies are being implemented to achieve this. Moreover, the supply of human islets for the clinic is quite limited, and we are now making pancreatic progenitors from pluripotent human embryonic stem cells as a much more reliable and larger source of surrogate cells for encapsulation and transplantation. [Clinical Trial Registration Number ACTRN12609000192280 (Australian and New Zealand Clinical Trials Registry)].

Keywords: Microcapsules, insulin-dependent diabetes, islets, pericapsular fibrotic overgrowth, embryonic stem cells, barium alginate, porcine islet-like cell clusters, fetal pancreas, transplantation, clinical trial.