Optimising islet engraftment is critical for successful clinical islet transplantation

Abstract

Clinical islet transplantation is currently being explored as a treatment for persons with type 1 diabetes and hypoglycaemia unawareness. Although 'proof-of-principle' has been established in recent clinical studies, the procedure suffers from low efficacy. At the time of transplantation, the isolated islets are allowed to embolise the liver after injection in the portal vein, a procedure that is unique in the area of transplantation. A novel view on the engraftment of intraportally transplanted islets is presented that could explain the low efficacy of the procedure.

The synthetic liver X receptor agonist GW3965 reduces tissue factor production and inflammatory responses in human islets in vitro

“…However, sustained insulin-independence after islet transplantation has been difficult to achieve [1], partly because of a significant loss of islets during brain death, islet isolation, transplantation and revascularisation in the liver [2,3]. Islet apoptosis may be induced by various stress factors such as hypoxia [4] and inflammation [5].…”

Endovascular Methods for Stem Cell Transplantation

“…The hypothesis is that the cells cannot perform diapedesis but are instead primarily forming a mural thrombus after, with low probability, being displaced against the blood flow into the arterial tree and then encapsulated by endothelial cells. The plaque formation can thereby provide capillary ingrowth, an absolute requirement for endocrine function (Korsgren et al 2008). Such a hypothesis would also shed further light on the low efficacy of portal transplantations methods.…”

“…Outside the CNS, other clinical trials with cell based therapies aimed at e.g. muscle dystrophy (Gussoni et al 1997;Miller et al 1997), ischemic heart disease (Stamm et al 2003), graft versus host disease (Le Blanc et al 2004;Ringden et al 2006) and type I diabetes mellitus (Scharp et al 1991;Shapiro et al 2000;Korsgren et al 2008) have yielded promising results. So far, many of the cell therapies are still in trials since both safety and effects must be thoroughly evaluated.…”

The isolated pancreatic islet as a micro-organ and its transplantation to cure diabetes

“…The second is pre-transplant treatment of islets with prolactin, a known angiogenic stimulant to islets. 78 (6) Loss of neural innervation prevents the neurally-mediated increase in islet perfusion during increased oxygen demand of glucose utilization occurring with stimulus-secretion coupling. This is likely not reversible given the geography of transplanted islets.…”