Revascularization of Transplanted Islets
Can It Be Improved?
- 1Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University, Nashville, Tennessee
- 2Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee
- 3VA Tennessee Valley Healthcare System, Nashville, Tennessee
- Corresponding author: Alvin C. Powers,
Pancreatic islets are highly vascularized, which is important in their ability to quickly secrete insulin in response to changes in blood glucose. Although pancreatic islets comprise only 1–2% of pancreatic mass, they receive 5–10% of pancreatic blood flow. Blood vessels within pancreatic islets are of a greater density than those in surrounding exocrine tissue and are lined with fenestrated endothelial cells. These specialized features are responsible for the greater partial pressure of oxygen in islets compared with acinar tissue and other organs, which is likely important for normal islet cell function. Islet production of angiogenic factors such as vascular endothelial growth factor-A (VEGF-A) and angiopoietin-1 is critical for creating this highly vascularized state (1,2). During embryonic development, reciprocal endothelial-endocrine cell signaling and the formation of functional blood vessels appear to instruct pancreatic differentiation and morphogenesis (3–5). Development of the islet vasculature is coordinated with islet formation, but blood flow to endocrine cells precedes their final assembly into a mature islet (2).
Pancreatic islet isolation severs the connections between the islet vasculature and the systemic circulation. In contrast with whole-organ transplantation, where organ perfusion is quickly reestablished by reconnection of arterial and venous vessels, the reestablishment of blood flow to transplanted islets requires several days and involves angiogenesis and possibly vasculogenesis. Not only are islets avascular for several days following transplantation, they are less vascularized and have a lower oxygen tension than islets in the pancreas when revascularization is complete (6,7). The death of significant numbers of islets in the days following transplantation …