Donor pigs for clinical islet xenotransplantation: Review and future directions

Abstract

Allogeneic islet transplantation becomes a viable option for patients with unstable type 1 diabetes. However, considering the huge number of patients with type 1 diabetes, human donor shortage is a serious issue. To overcome the donor shortage issue, xenotransplantation is an attractive option. In fact, clinical islet xenotransplantation has been conducted since 1990s. The first clinical trial was performed using fetal pigs and demonstrated the porcine pancreatic tissue could survive in human body with immunosuppressive strategies. To scale up the islet production, Canadian group established a method for islet isolation from neonatal pigs. Their method has been used for clinical islet xenotransplantation in New Zealand, Russian, Mexico, Argentina, and China. Recently Korean group published a clinical protocol for islet xenotransplantation using adult pigs. For the next generation of islet xenotransplantation, gene-modified pigs were created. Especially "superislets" created by Belgian group demonstrated promising preclinical outcomes. With advanced donor pigs, islet xenotransplantation might become a suitable treatment for the majority of type 1 diabetic patients.

Keywords: clinical trials; islet transplantation; islets; xenotransplantation.

Graphical Abstract

Pig Pancreas from Fetus Neonatal Adult Gene modified

Figure 1.

The chamber system for islet macroencapsulation and encapsulated porcine islets described by Dresden team. The system is built from two islet modules containing the islets immobilized in alginate, and central oxygen module. Oxygen-enriched gas mixture (95% oxygen) is directly injected into central oxygen module, and oxygen is delivered into islet modules. This system allows islet survival due to avoiding the ischemic issue.