Microencapsulation for the cell and molecular therapy of type 1 diabetes mellitus: actual state and future perspectives between promise and progress.

The history of microencapsulation of live cells starts from an old idea of Thomas M. S. Chang in 1964, thereafter applied to isolated pancreatic islets by Anthony M. Sun in 1980. The original aim was to provide isolated cells with an immune-protective shield, to prevent physical contact between the transplanted cells and the host's immune system, with retention of the microcapsules' biocompatibility and physical-chemical properties over time. In particular, this revolutionary approach essentially applied to islet grafts, in diabetic not immunosuppressed recipients, at pre-clinical (rodents), and subsequently clinical level. Among the different chemistries potentially suitable for microencapsulation of live cells, alginic acid (AG)-based polymers, originally proposed by Sun, proved to be superior to all others, in the following decades. In fact, only AG-based microcapsules, containing allogeneic islets, ultimately entered pilot human clinical trials in patients with type 1 diabetes mellitus, since immuno-selectiveness and biocompatibility of AG-hydrogels were never matched by other biopolymers. With problems related to human islet procurement coming into a sharper focus, in conjunction with technical limits of the encapsulated islet grafting procedures, new challenges are actually being pursued, with special regard to developing both, new cellular systems, able to release immunomodulatory molecules and insulin itself, and new microencapsulation methods, with use of novel polymeric formulations, under actual scrutiny. Use of embryonic and adult stem cells, within microcapsules, should address the restricted availability of cadaveric human donor-derived islets, while a new generation of newly-engineered microcapsules could better fulfil issues with graft site and long-term retention of biopolymer properties.