Long‐term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques

Abstract

Although human islet transplantation has proven to provide clinical benefits, especially the near complete amelioration of hypoglycemia, the supply of human islets is limited and insufficient to meet the needs of all people that could benefit from islet transplantation. Porcine islets, secreting insulin nearly identical to that of human insulin, have been proposed as a viable supply of unlimited islets. Further, encapsulation of the porcine islets has been shown to reduce or eliminate the use of immunosuppressive therapy that would be required to prevent rejection of the foreign islet tissue.The goal of the current study was to determine the long-term safety and efficacy of agarose encapsulated porcine islets (macrobeads) in diabetic cynomolgus macaques, in a study emulating a proposed IND trial in which daily exogenous insulin therapy would be reduced by 50% with no loss of glucose regulation. Four of six animals implanted with macrobeads demonstrated ≥ 30% reduction in insulin requirements in year 1 of follow-up. Animals were followed for 2, 3.5, and 7.4 years with no serious adverse events, mortality or evidence of pathogen transmission. This study supports the continued pursuit of encapsulated porcine islet therapy as a promising treatment option for diabetes mellitus.

A porcine islet-encapsulation device that enables long-term discordant xenotransplantation in immunocompetent diabetic mice

“… 75 , 76 , 77 , 78 Therefore, porcine islets are assumed to show low survival. In contrast, when porcine islets are transplanted into monkey diabetes models or humans, efficacy has been observed at 10,000–20,000 IEQ/kg, 11 , 12 , 79 , 80 which is higher than, but not so different from, that of islet transplantation from human donors to humans (5,000–15,000 IEQ/kg). Although the mechanism has not been fully elucidated, there seems to be a large species difference.…”

Xenotransplantation of pig islet cells: Potential adverse impact of virus infections on their functionality and insulin production

“…Porcine viruses had not been transmitted to the recipients in some preclinical trials transplanting pig islet cells into non‐human primates were a virus screening was performed 10,14–16 and in all clinical trials using pig islet cells performed until now 17–25 . In one preclinical trial, 10 and in most clinical trials, 17–21,23 microencapsulated islet cells from Auckland Island pigs were used, a pig strain, which is well characterized microbiologically.…”