A porcine islet-encapsulation device that enables long-term discordant xenotransplantation in immunocompetent diabetic mice.

Islet transplantation is an effective treatment for type 1 diabetes (T1D). However, a shortage of donors and the need for immunosuppressants are major issues. The ideal solution is to develop a source of insulin-secreting cells and an immunoprotective method. No bioartificial pancreas (BAP) devices currently meet all of the functions of long-term glycemic control, islet survival, immunoprotection, discordant xenotransplantation feasibility, and biocompatibility. We developed a device in which porcine islets were encapsulated in a highly stable and permeable hydrogel and a biocompatible immunoisolation membrane. Discordant xenotransplantation of the device into diabetic mice improved glycemic control for more than 200 days. Glycemic control was also improved in new diabetic mice "relay-transplanted" with the device after its retrieval. The easily retrieved devices exhibited almost no adhesion or fibrosis and showed sustained insulin secretion even after the two xenotransplantations. This device has the potential to be a useful BAP for T1D.

Graft failure after allogeneic islet transplantation in a patient with type 1 diabetes and a high anti-glutamic acid decarboxylase antibody titer.

Pancreatic islet transplantation is a ß-cell replacement therapy for people with insulin-deficient diabetes who have difficulty in glycemic control and suffer from frequent severe hypoglycemia. However, the number of islet transplantations carried out is still limited in Asia. We report a case of allogeneic islet transplantation in a 45-year-old Japanese man with type 1 diabetes. Although the islet transplantation was successfully carried out, graft loss was observed on the 18th day. Immunosuppressants were used in accordance with the protocol, and donor-specific anti-human leukocyte antigen antibodies were not detected. Autoimmunity relapse was also not observed. However, the patient had a high titer of anti-glutamic acid decarboxylase antibody from before the islet transplantation, and autoimmunity might thus have affected the ß-cells in the transplanted islet. The evidence is still scarce to reach conclusions, and further data accumulation is required to enable proper patient selection before islet transplantation.

Quality of life after total pancreatectomy with islet autotransplantation for chronic pancreatitis in Japan.

BACKGROUND: Patients with chronic pancreatitis (CP) often have severe and intractable abdominal pain, leading to decreased quality of life (QOL), inability to work or attend school, and increased health care costs due to repeated emergency room visits and hospitalizations. METHODS: We evaluated the efficacy of total pancreatectomy and islet autotransplantation (TPIAT) in terms of pain control and QOL in CP patients treated at our center in Japan. To evaluate QOL, we used the Short-Form 36 Health Survey version 2 (SF-36v2® Standard, Japanese), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and Quality of Life Questionnaire-Pancreatic Modification (QLQ-PAN28). RESULTS: Between August 2016 and June 2019, we performed this procedure in 5 patients. All patients were followed up for 12 months and all transplanted islets were still functioning at the 1-year follow-up. The major adverse events were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization; no case had sequelae. No major complications were due to islet transplantation. Pain scores improved postoperatively in all patients. Three QOL item dimensions role-physical (p = 0.03125), general health perception (p = 0.03125) and vitality (p = 0.03125) in the SF-36 were significantly improved 12 months after TPIAT. Mean values of many other QOL items improved, though not significantly. CONCLUSION: The QOL improvement after TPIAT for CP suggests its effectiveness in the Japanese population.

Allogeneic islet transplantation with monitoring of islet-specific cellular autoimmunity in a Japanese patient with type 1 diabetes: A case report.

Here, we report a case of allogeneic islet transplantation in Japan. A 48-year-old man received intraportal islet transplantation (5,945 islet equivalent/kg), and stabilization of blood glucose levels and suppression of hypoglycemia were achieved. In the present case, we used our original assessment method to detect the responses of the recipient's T cells to islet autoantigens over time to monitor cellular autoimmunity. Other markers could not predict graft dysfunction in advance, but our method detected the activation of islet antigen-specific CD8+ T-cell responses before the deterioration of pancreatic ß-cell function, indicating the possibility of the non-invasive detection of pancreatic ß-cell damage due to recurrent autoimmunity.