[show abstract][hide abstract] ABSTRACT: We are reporting first successful intrahepatic autologous islet transplantation after total pancreatectomy in a patient with chronic pancreatitis and primary sclerosing cholangitis.
Total pancreatectomy and subsequent islet autotransplantation were performed in a 16-year-old boy with intractable pain due to chronic pancreatitis in the setting of ulcerative colitis and primary sclerosing cholangitis (PSC). Liver biopsy revealed PSC with focal bridging fibrosis. The pancreas was surgically removed and digested, and islets were isolated, highly purified, and infused intraportally.
Over 18-month follow-up, the patient did not show progression of chronic liver disease or signs of portal hypertension. Magnetic resonance cholangiopancreatography revealed no new changes, and liver biopsy did not show progression of the periportal fibrosis. Pain medication was weaned over 12 months at which time glycemic control was excellent without exogenous insulin supplementation. HbgA1c was 5.9. Fifteen months after the procedure, stimulation with a mixed meal led to a fourfold increase of serum C-peptide and an eightfold increase of insulin level.
Pancreatic autologous islets can be successfully transplanted into a liver affected by PSC without compromising hepatic or graft function. Durability of the procedure may be limited in the future by the natural course of the liver injury caused by PSC.
Journal of Gastrointestinal Surgery 12/2013; · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: To develop a novel approach for local immunoprotection using CD4(+)CD25(high)CD127(-) T regulatory cells (Tregs) attached to the surface of the islets before transplantation.
Tregs expanded ex vivo can control allo and autoreactivity, therefore, Treg-based therapy may offer more effective protection for transplanted islets from immunologic attack than currently used immunosuppression. Local application of Tregs can make such therapy more clinically feasible and efficient.
Human islets were isolated and coated with allogeneic ex vivo expanded Tregs using biotin-poly(ethylene glycol)-N-hydroxysuccinimide ester (biotin-PEG-NHS) and streptavidin as binding molecules.
Coating pancreatic islets with Tregs did not affect islet viability (>90% fluorescein diacetate/propidium iodide) or the insulin secretion profile in dynamic islet perifusion assays. After in vitro incubation with allogeneic T effector cells, Treg-coated islets revealed preserved function with higher insulin secretion compared with controls-native islets, coated islets with T effector cells or when Tregs were added to the culture, but not attached to islets (P < 0.05). In addition, the Enzyme-linked immunosorbent spot (ELISPOT) assay revealed suppression of interferon (IFN)-γ secretion, when T effector cells were challenged with Treg-coated islets comparing to controls (99 ± 7 vs 151 ± 8 dots, respectively; P < 0.01).
We demonstrated, for the first time, the ability to bind immune regulatory cells to target cells with preservation of their viability and function and protective activity against immune attack. If successfully tested in an animal model, local delivery of immunoprotective Tregs on the surface of transplanted pancreatic islets may be an alternative or improvement to the currently used immunosuppression.
Annals of surgery 09/2011; 254(3):512-8; discussion 518-9. · 7.90 Impact Factor