Current situation of clinical islet transplantation from allogeneic toward xenogeneic

Abstract

Currently, type 1 diabetes requires lifelong insulin injection and careful blood glucose control to prevent secondary complications, but islet transplantation could make a type 1 diabetic patient insulin independent. On the other hand, islet transplantation needs human donors and donor shortage is the most serious issue. To alleviate the donor shortage, non‐heart‐beating and living donors were used; in addition, the efficacy of islet isolation and transplantation has been improved. However, the donor shortage issue will not be solved as long as human donors are the only source. To solve the donor shortage issue, islet xenotransplantation using porcine islets was initiated in 1994. Islet xenotransplantation has a potential to cure many type 1 diabetic patients, although there is the risk of developing serious or novel infection. Therefore, the World Health Organization has been interested in xenotransplantation, and the International Xenotransplantation Association (IXA) has published consensus statements to initiate xenogeneic islet transplantation. Clinical islet xenotransplantation was conducted under the official regulation, and safety and efficacy data have been accumulated. Currently an efficient method to overcome xenorejection is an important research target. In addition to traditional immunosuppressive drugs and immune isolation methods, the gene modification with CRISPR and blastocyst complementation have been investigated with promising outcomes. Once the xenorejection issue is overcome, islet xenotransplantation should become a curative treatment for type 1 diabetic patients.

Long‐term follow‐up for the microbiological safety of clinical microencapsulated neonatal porcine islet transplantation

“…Allogeneic islet transplantation has become a viable treatment for unstable type 1 diabetic patients 1 . On the other hand, donor shortage is a serious issue and xenotransplantation, especially using porcine organ, is a promising approach to remedy this situation 2,3 …”

β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells?

“…Current pharmacological treatments for T1DM mostly rely on daily injections of exogenous insulin to control glycemia or whole pancreas and islet cell transplantation as an alternative [ 10 ]. The islet transplantation approach is circumscribed by a serious scarcity of donor tissues and a potential risk of tissue rejection [ 11 ]. Generation of transplantable human β-cells from human pluripotent stem cells, such as embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC), is an ultimate goal of stem cell therapeutics.…”

Pancreas transplantation for type 1 diabetes in Japan: past, present and future prospects

“…To overcome the shortage of available human pancreata, there have been considerable efforts seeking alternative islets sources, such as xenogeneic islets, human embryonic stem cells (hESCs), and induced pluripotent stem cells (iPSCs). Among them, porcine islets are considered the most advanced and promising sources of islets for transplantation based on the long history of clinical trials and accumulated safety and efficacy data, while hESCs-derived β cells have only limited clinical data, and no clinical data are available regarding iPSCsderived β cell transplantation (11,12).…”

“…Although porcine islet xenotransplantation for humans has been reported to be less effective than allogeneic islet transplantation (12), that has the advantage of providing an unlimited supply of fresh, uniformly quality-controlled islets from medical-grade pigs. Furthermore, porcine insulin differs from human insulin in only a single amino acid residue and was used to treat diabetes in humans for many years before the start of human insulin treatment from the 1980s.…”