Chronic diabetes harms islet-cell transplants by inhibiting graft vascularisation

Pancreatic islet-cell transplantation is very effective in treating insulin-dependent diabetes in animals but has had no success in humans. Most animals have received islet-cell grafts after short periods of diabetes, while patients have been grafted after years of disease. We have shown a detrimental effect of chronic diabetes on islet-cell grafts in animals, which is at least partially ameliorated by peritransplant insulin infusion. We suggest that this detrimental effect may be mediated by poor vascularisation. There is further evidence from wound healing and tumour grafting experiments, and from the recent insulin pump studies in humans to support our hypothesis. To be successful, islet-cell grafts in humans may have to be performed earlier in the course of the disease and be preceded by a period of accurate diabetic control.