The liver is the preferred site for islet transplantation (ITx) but not ideal due to limitations affecting engraftment.
We evaluated the safety and efficacy of ITx in the omentum using a resorbable biological scaffold in 3 subjects with type 1 diabetes and negative C-peptide. Islets were combined with autologous plasma and thrombin to generate a biologic scaffold and layered laparoscopically on the omentum. Induction was with anti-thymocyte globulin and etanercept. Maintenance was with mycophenolate sodium and tacrolimus. Demographics, islet dose and metabolic data are shown in the Table.
| Subject # | Age (years) | Duration T1DM (years) | BMI (Kg/m2) | IEQ†/Kg | MMTT‡ Stimulated Glucose (mg/dl)/C-peptide (ng/ml) | Insulin dose U/Kg/day (Units/day) | HbA1c% | ||||
| 6 months | 12 months | 24 months | Pre-ITx | Latest | Pre-ITx | Latest | |||||
| 1 | 43 | 26 | 21.5 | 11,386 | 181/3.32 | 277/1.79 | 317/0.49 | 0.62 (33) | 0.14 (7) | 6.8 | 5.3 |
| 2 | 32 | 16 | 25.3 | 9,635 | 372/0.88 | 374/0.65 | 332/0.52* | 0.45 (31) | 0.45 (30) | 5.7 | 5.6 |
| 3 | 46 | 42 | 24 | 12,648 | 277/2.47 | - | - | 0.45 (20) | 0.2 (11) | 6.3 | 6.3 |
| * 18 months Post-ITx † IEQ= islet equivalents ‡ MMTT = mixed meal tolerance test | |||||||||||
| Subject # | Age (years) | Duration T1DM (years) | BMI (Kg/m2) | IEQ†/Kg | MMTT‡ Stimulated Glucose (mg/dl)/C-peptide (ng/ml) | Insulin dose U/Kg/day (Units/day) | HbA1c% | ||||
| 6 months | 12 months | 24 months | Pre-ITx | Latest | Pre-ITx | Latest | |||||
| 1 | 43 | 26 | 21.5 | 11,386 | 181/3.32 | 277/1.79 | 317/0.49 | 0.62 (33) | 0.14 (7) | 6.8 | 5.3 |
| 2 | 32 | 16 | 25.3 | 9,635 | 372/0.88 | 374/0.65 | 332/0.52* | 0.45 (31) | 0.45 (30) | 5.7 | 5.6 |
| 3 | 46 | 42 | 24 | 12,648 | 277/2.47 | - | - | 0.45 (20) | 0.2 (11) | 6.3 | 6.3 |
| * 18 months Post-ITx † IEQ= islet equivalents ‡ MMTT = mixed meal tolerance test | |||||||||||
Subject 1 was insulin independent for 15 months and maintains stable glycemic control. Subject 2 had marginal graft function with persistence of severe hypoglycemia (SH) and then underwent intrahepatic ITx resulting in insulin independence. Subject 3 had a 55% reduction in insulin dose and maintains excellent glycemic control.
Our initial experience demonstrates feasibility and safety of ITx on the omentum. Graft function persisted throughout follow-up (6-24 months) resulting in improved glycemic control and absence of SH (subjects 1 and 3).
Results suggest a significant loss of islets early post-ITx followed by gradual functional decline similar to intrahepatic ITx. Strategies to improve oxygen delivery and neo-vascularization and minimize immunosuppression are needed to improve long-term outcomes at this site.
D. Baidal: None. C. Ricordi: None. D.M. Berman: Stock/Shareholder; Self; Pfizer Inc. A. Pileggi: Stock/Shareholder; Self; Converge Biotech, Inc.. Stock/Shareholder; Spouse/Partner; Converge Biotech, Inc. A.M. Alvarez Gil: None. N. Padilla: None. G. Ciancio: None. E. Linetsky: None. R. Alejandro: None.
