RESUMEN
To comply with regulatory restrictions, with regard to graft of human islets immunoprotected within artificial microcapsules, into patients with type 1 diabetes mellitus (T1DM) with no recipient immunosuppression, we have prepared standard protocols on: (1) sodium alginate purification (clinical grade) for microcapsule fabrication; (2) preparation of biocompatible and permselective microcapsules containing human islets; and (3) minimally invasive techniques for grafting of the encapsulated human islets into the recipients' peritoneal cavity. As to no. 1, starting from pharmaceutical grade, raw sodium alginate powder, we prepared a pyrogen- and endotoxin-free 1.6% alginate solution by means of dialysis, multiple filtrations, and dilution/osmolality adjustments. As to no. 2, we have selected human islet preparations associated with >80% purity/viability, which underwent careful functional quality control testing prior to encapsulation; namely, most capsules contained one islet. As for no. 3, we have devised a simple intraperitoneal injection method under abdominal echography guidance with only local anesthesia to deposit the encapsulated islets in saline within the peritoneal leaflets. These technical protocols were officially approved by the Italian Ministry of Health which has released permission to conduct a phase I, closed human trial in 10 patients using encapsulated human islet grafts into nonimmunosuppressed patients with T1DM.