Dataset Information

Transplantation of macroencapsulated human islets within the bioartificial pancreas ?Air to patients with type 1 diabetes mellitus.

ABSTRACT: Macroencapsulation devices provide the dual possibility of immunoprotecting transplanted cells while also being retrievable, the latter bearing importance for safety in future trials with stem cell-derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The ?Air device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the ?Air device containing allogeneic human pancreatic islets into patients with type 1 diabetes. Four patients were transplanted with 1-2 ?Air devices, each containing 155 000-180 000 islet equivalents (ie, 1800-4600 islet equivalents per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the ?Air device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the ?Air device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited (Clinicaltrials.gov: NCT02064309).

SUBMITTER: Carlsson PO

PROVIDER: S-EPMC6055594 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus.

Carlsson Per-Ola PO Espes Daniel D Sedigh Amir A Rotem Avi A Zimerman Baruch B Grinberg Helena H Goldman Tali T Barkai Uriel U Avni Yuval Y Westermark Gunilla T GT Carlbom Lina L Ahlström Håkan H Eriksson Olof O Olerud Johan J Korsgren Olle O

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20180202 7

Macroencapsulation devices provide the dual possibility of immunoprotecting transplanted cells while also being retrievable, the latter bearing importance for safety in future trials with stem cell-derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic ...[more]

PMID: 29288549

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Project description:OBJECTIVE:Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS:This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant. RESULTS:The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS:Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.

Dataset Information

Transplantation of macroencapsulated human islets within the bioartificial pancreas ?Air to patients with type 1 diabetes mellitus.

Publications

Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus.

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