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Pancreatic islet transplantation to the liver: how can vascularization problems be resolved?

Joey Lau, Guangxiang Zang & Per-Ola Carlsson

Pancreatic islet transplantation to the liver provides the possibility of restoring glucose homeostasis in patients with Type 1 diabetes. However, several hurdles remain to be solved in order to optimize this treatment, including developing the means to restrict early islet cell death by hypoxia and inflammatory events and to facilitate the engraftment of islets by improvements in revascularization. Intraportally transplanted islets are poorly revascularized in contrast to islets implanted into muscle or the pancreas. Changing the implantation organ may therefore be a possibility for improving results in clinical islet transplantation, but other hurdles may then arise, including the issue of overload and excessive islet cell death when implanting islets in clusters. New strategies to improve revascularization, also at the intraportal site, by proangiogenic factors such as VEGF, and by inhibition of angiostatic factors such as thrombospondin-1 present in islets, or by cell therapy using mesenchymal stem cells or endothelial progenitor cells bound to the islet surface, provide possible solutions.