The long road to pancreatic islet transplantation

Abstract

Some of us (MAH) have known Dr. Eric Rose when he was a resident, a fellow in cardiothoracic surgery, the director of heart transplantation program, the director of Cardiothoracic Division, and finally as Valentine and Johnson and Johnson Professor and Chairman of Department of Surgery at Columbia University for the last 15 years. Having this long relationship with Dr. Rose, I was not sure where or how to begin this tribute to my former resident, colleague, collaborator, and eventually director. It was as an innovative and courageous Chairman that Dr. Rose had a major impact on me when he appointed me as a Residency Program Director and through his remarkable interest and support of educational changes led to a rebirth and growth of the surgical residency at Columbia NY Presbyterian Hospital to one of the leading programs in the country. But the greatest inspiration that Dr. Rose brought to the Department of Surgery was his fearless and relentless support of ventures into the unknown. When faced with heart transplantation as a junior faculty member, he went on to lay the foundation for the largest heart transplant program in the world; when challenged by development and lack of acceptance of Left Ventricular Assist Devices, he guided their approval following appropriate multiinstitutional studies which led to their adoption as standard of care. His influence extended to the support of a Pancreatic Islet Transplantation Program, originally inspired by his predecessor and mentor, Dr. Keith Reemtsma. Doctor Rose invested and encouraged both the clinical and experimental development of this program under my guidance as part of his dedication to innovation.

Figure 1. Blood Glucose Levels in Transplanted Rodents

(A) Figure presents mean fasting serum glucose level in animals within the 60 days follow-up. Mean fasting glucose level oscillates below 110 mg/dL for animals from group 1 (gel + VEGF/PDGF), whereas in other groups it was statistically higher, ANOVA, p<0.05. As an additional control, removal of the scaffolds in normoglycemic animals from the gel + VEGF/PDGF group on day +60 led to prompt return of diabetes and hyperglycemia. Error bars represent S.E.M. (B) Islet grafting success rate. Number of animals out of six total achieving euglycemia following syngeneic islet transplantation is shown on the Y axis. Euglycemia was defined as four-hour fasting glucose < 110 mg/dL on post transplant days +5 through +60. The statistical significance of the differences in grafting success rate among the different treatment groups is shown and was determined by ANOVA using the blood glucose measurements obtained in the 55 day post transplant window.

Figure 2. Representative coronal plane of abdomen of Lewis Rats transplanted with allogeneic islets

Rats were imaged (90 min) dynamically with 250 uCi [11C]DTBZ and a Concorde microPET scanner. The large high uptake area in the top center of the figure is a plane of the liver, an organ of [11C] DTBZ catabolism. Radioligand uptake in the form of a ring corresponds to the location of the transplanted islets. Following imaging, the presence of insulin staining cells in this location was confirmed by preparing paraffin embedded sections of the tissue and insulin staining by immunohistochemistry.