Human islet isolation and allotransplantation in 22 consecutive cases

Abstract

This report provides our initial experience in islet isolation and intrahepatic allotransplantation in 21 patients. In group 1, 10 patients underwent combined liver-islet allotransplantation following upper-abdominal exenteration for cancer. In group 2, 4 patients received a combined liver-islet allograft for cirrhosis and diabetes. One patients had plasma C-peptide greater than 3 pM and was therefore excluded from analysis. In group 3, 7 patients received 8 combined cadaveric kidney-islet grafts (one retransplant) for end-stage renal disease secondary to type 1 diabetes mellitus. The islets were separated by a modification of the automated method for human islet isolation and the preparation were infused into the portal vein. Immunosuppression was with FK506 (group 1) plus steroids (groups 2 and 3). Six patients in group 1 did not require insulin treatment for 5 to greater than 16 months. In groups 2 and 3 none of the patients became insulin-independent, although decreased insulin requirement and stabilization of diabetes were observed. Our results indicate that rejection is still a major factor limiting the clinical application of islet transplantation in patients with type 1 diabetes mellitus, although other factors such as steroid treatment may contribute to deteriorate islet engraftment and/or function.

Figure 1

Modified automated procedure for islet separation. (A) Lines that are occluded during the recirculation phase; (B) lines that are occluded during the dilution phase. In the first phase, collagenase solution recirculates in a closed system, in which the collagenase solution and the pancreas are progressively heated to 37°C. In a second phase, the islets that are progressively released from the digesting pancreas are saved in collecting flasks or bottles.

Figure 2

Plasma glucose and daily insulin requirements of a cluster-islet patient (group 1, No.1, Tables 1 and 2), who is still insulin independent over 16 months following liver-islet allotransplantation.

Figure 3

Plasma glucose and insulin requirements in patient No. 1 (group 1, Tables 1 and 2) during the first postoperative week, demonstrating an episode of significant insulin resistance in which over 2000–3000 units i.v. per day were administered.

Figure 4

Plasma glucose and daily insulin requirements before and after human islet allotransplantation in one type 1 diabetic patient who received a combined liver-islet graft (group 2, No.1, Tables 1 and 2).

Figure 5

Plasma glucose and C-peptide following Sustacal Tolerance Test (STT) before and 2, 3, and 6 months after human islet allotransplantation (group 2, No.1, Tables 1 and 2).

Figure 6

Plasma glucose and daily insulin requirements in a type 1 diabetic recipient of combined liver-islet allograft (group 2, No.2, Tables 1 and 2). Insulin requirement rapidly decreased during the first 3 weeks following transplantation. A rejection episode in week 4 imposed a significant increment in the daily insulin dose, which never returned to prerejection levels.

Figure 7

Plasma glucose and daily insulin requirements in a type 1 diabetic patient who received a combined kidney-islet allograft (group 3, No.1, Tables 1 and 2). Daily insulin requirement decreased by 48% in the first 40 weeks posttransplant, compared with pretransplant requirements.

Figure 8

Basal and stimulated plasma C-peptide levels in patients following kidney-islet (n=7), liver-islet (n=2), and cluster-islet (n=9) allotransplantation. C-peptide appears higher in cluster-islet patients than in liver-islet and kidney-islet recipients.