Clinical islet transplantation in Japan

Department of Surgery, Chiba-East National Hospital, National Hospital Organization, Chiba City, Chiba, Japan.
Journal of Hepato-Biliary-Pancreatic Surgery (Impact Factor: 1.6). 02/2009; 16(2):124-30. DOI: 10.1007/s00534-008-0020-3
Source: PubMed

ABSTRACT The results of clinical islet transplantation in Japan are, here in, reported and discussed its efficacy and problems.
Since the first islet transplantation was performed in 2004, 65 islet isolations and 34 islet transplantations to 18 type 1 diabetic patients have been performed in Japan.
Following islet transplantation, patients experienced decreased insulin requirements and lower hemoglobin A1C levels, and positive serum C-peptide levels. All patients achieved stabilized blood glucose levels and the disappearance of hypoglycemic unawareness. Although three patients achieved insulin independency for a limited period, persistent islet graft function was difficult to maintain. Overall islet graft survival was 86.5% at 6 months, 78.7% at 1 year, and 62.9% at 2 years after the first islet transplantation. In our institution, we carried out 23 islet isolations and six islet transplantations to four patients. Although insulin independency was not achieved, all patients showed a disappearance of hypoglycemic unawareness.
Using data from the Japanese Trial of Islet Transplantation, the effectiveness of islet transplantation was shown even when using the pancreata from non-heart-beating donors. Although there are a number of problems to be solved and further improvement is needed, we can state that the introduction of clinical islet transplantation offers hope for type 1 diabetic patients.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite modern medical breakthroughs, diabetes mellitus is a worldwide leading cause of morbidity and mortality. Definitive surgical treatment of diabetes mellitus was established with the advent and refinement of clinical pancreas transplantation in the 1960s. During the following decades, critical discoveries involving islet isolation and engraftment took place. Clinical islet cell transplantation represents the potential for reduced insulin requirements and debilitating hypoglycemic episodes without the morbidity of surgery. Unfortunately, islet cell transplantation was unable to achieve comparable results with solid organ transplantation. This was until the Edmonton protocol (steroid-free immunosuppression) was described, which demonstrated that islet cell transplantation could be a viable alternative to pancreas transplantation. Significant advances in islet purification techniques and novel immunomodulatory agents have since renewed interest in islet cell transplantation. Yet the field is still challenged by a limited supply of islet cells, inadequate engraftment, and the deleterious effects of chronic immunosuppression. This article discusses the history and the current status of clinical islet cell transplantation.
    Seminars in Interventional Radiology 06/2012; 29(2):90-8. DOI:10.1055/s-0032-1312569
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This cross-sectional study based on self-administrated questionnaire was conducted to investigate knowledge, related factors, and sources of information regarding islet transplantation in patients with type 1 diabetes in Japan. Among 137 patients who provided valid responses, 67 (48.9%) knew about islet transplantation. Their main source of information was newspapers or magazines (56.7%) and television or radio (46.3%). However, 85.8% of patients preferred the attending physician as their source of information. Although more than half of the patients were correctly aware of issues related to islet transplantation, the following specific issues for islet transplantation were not understood or considered, and there was little knowledge of them: need for immunosuppressants, lifestyle and dietary adaptations, fewer bodily burdens, and complications. The experience of hypoglycaemia, a high level of academic background, frequent self-monitoring of blood glucose, and the use of continuous subcutaneous insulin infusion were related to higher knowledge about islet transplantation.
    Journal of Transplantation 11/2011; 2011:136298. DOI:10.1155/2011/136298
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cryopreservation is necessary for the long-term storage of islet cells and to increase the practicality of clinical islet transplantation. Fetal bovine serum (FBS) supplemented with 10% dimethyl sulfoxide (DMSO) is generally used as a freezing medium for islet cells. However, FBS should ideally be avoided in cell culture and transplantation because of recent animal health problems, such as bovine spongiform encephalopathy and viral infections. The aim of this study was to develop a new serum-free freezing medium by examining the effectiveness of the silk protein sericin, which is produced by Bombyx mori. Islets prepared from Lewis rats by collagenase digestion and Histopaque gradient centrifugation, followed by culture in medium containing 0.1% sericin for 3 days, were cryopreserved using 0.1, 0.5, 1, 2, and 5% sericin or FBS. DMSO (1, 4, 7, 10, and 15%) was added to the medium as a cryoprotectant. After thawing, on days 1, 4, 7, and 14, viable islets were counted in order to evaluate their survival. Insulin secretion was measured in vitro by a static incubation test on day 4. The in vivo function of cultured islets was tested by syngeneic transplantation. Islets were evaluated histologically and immunohistochemically after transplantation. There were no significant differences between freezing medium containing 1% sericin and that containing 10% FBS with regard to the survival rate of islets and stimulated insulin secretion. Following transplantation, islets rapidly reversed hyperglycemia and maintained normal glycemic control. In addition, the use of 7% DMSO as a cryoprotectant with sericin showed the same results as higher DMSO concentrations with FBS. The present results showed that serum-free medium containing sericin is useful for both cryopreservation and cell culture.
    Journal of Hepato-Biliary-Pancreatic Sciences 06/2011; 19(4):354-60. DOI:10.1007/s00534-011-0415-4 · 2.31 Impact Factor