Alginate microcapsules for pancreatic islet cell graft immunoprotection: struggle and progress towards the final cure for type 1 diabetes mellitus

Abstract

Lights and shadows have been associated with the use of alginate/polyaminoacidic microcapsules for transplantation of pancreatic islet cells for the therapy of diabetes mellitus, with no recipient pharmacological immunosuppression. In fact, preliminary success in rodents has generally not matched the results achieved in diabetic higher mammals. The restricted availability of cadaveric human donor organs/tissue, coupled to regulatory hurdles in the use of microcapsules in patients, has significantly delayed the progress of microencapsulated islet grafts into pilot clinical trials. While the basic formulation of microcapsules from the author’s laboratory, originally comprised of an alginate gel (AG) core, a double poly-L-ornithine (PLO) coat and an outer AG coat, has virtually remained unchanged, highly purified ‘clinical grade’ AG has been introduced in order to try to surmount regulatory restrictions. In parallel, novel insulin-producing cell types have been employed to fill the capsules, with particular regard to non-human tissue, such as adult and, more recently, neonatal porcine islets. In particular, using neonatal porcine islets enveloped in AG-PLO microcapsules, hyperglycaemia has been corrected in several diabetic animal models. Should standardisation and optimisation problems associated with both AG procurement and other membrane physical–chemical fabrication parameters be surmounted, microcapsules containing either human or, possibly, pig islets, could be close to approval for Phase I human clinical trials.

• blood glucose
• cells
• immunity
• insulin
• therapy