Islet transplantation for type 1 diabetes is a minimally invasive cell therapy. It was first introduced to the world in 1974, but the results were poor. The Edmonton protocol in 2000 and the subsequent CIT protocol significantly improved the outcome. In Japan as well, clinical application has been promoted since 1997 by the Japan Pancreas and Islet Transplant Association (JPITA). Initially, as in the rest of the world, the long-term survival rate of islets was low using the Edmonton protocol. Thereafter, the results were significantly improved using the CIT protocol. Finally, islet transplantation was covered by insurance in 2020 in Japan. Future issues include the indications for pancreas transplantation and islet transplantation in patients with type 1 diabetes, the distribution of donor pancreases to pancreas transplantation, islet transplantation, and medical costs. Islet transplantation is expected to develop into xenotransplantation and iPS cell transplantation in the future.

Islet transplantation is a minimally invasive and safe therapy for type1 diabetes mellitus patients with severe hypoglycemic unawareness. Multicenter clinical trials in Japan have confirmed that islet transplantation is effective for restoration of hypoglycemic awareness and reduction in the glycated hemoglobin level. Based on the results of clinical islet transplantation to date, islet transplantation was covered by public medical insurance in April 2020. This paper introduces the process of medical insurance coverage and outlines the facility requirements for implementation as an insured medical treatment.

In Japan, islet transplantation was covered by the national insurance system in 2020 after a transitional period with the special insurance system, named the “Advanced Medical Treatment B”, which had started in 2012. During the transitional period, 22 donors donated islets and 17 of them were actually transplanted. All the recipients have been able to maintain stable blood glucose levels, and severe hypoglycemic attacks have been successfully avoided. Based on the results of a multicenter clinical trial in Japan, pancreatic islet transplantation was covered by public medical insurance in April 2020. As a requirement for insurance coverage, the presence of a donor coordinator is now mandatory for certification as an islet transplant facility. The employment and education of coordinators will be an important aspect in the development of islet transplantation. Offering a new option of treatment for the patient with type I diabetes is the job assigned to the recipient transplant coordinator (RTC). For this purpose, an RTC is considered indispensable. In our institution, one individual has served as the RTC from the beginning of the program, and that person could offer peace of mind to patients. In this article, we would like to summarize the process of the establishment of coordinators for islet transplantation with current problems and future perspectives.

Islet transplantation is an effective treatment for insulin-dependent diabetes mellitus, but the shortage of donors is a problem. To solve this problem, porcine islets have been widely studied as an alternative cell source. This paper focuses on recent advances in porcine islet transplantation, especially transgenic porcine, islet encapsulation, and biological safety. So far, genetic modifications aimed at reducing the immunogenicity of porcine islet cells, prolonging the survival time of grafts, and improving insulin secretory function have been reported. Microencapsulation or macroencapsulation of porcine islets may suppress rejection with little or no immunosuppression. In addition, the risk of endogenous retrovirus infection in pigs is considered low due to the absence of infection in some clinical and preclinical studies. Appropriate pig selection, pathogen screening, and quality control can improve the safety and efficacy of porcine islet transplantation in future clinical trials, and porcine islet transplantation is expected to be put into practical use thereafter.

Pancreatic islet transplantation is an ideal minimally invasive treatment for patients with severe type 1 diabetes who suffer from glycemic control. However, it is crucial for islet transplantation to combine with regenerative medicine to expand this attractive treatment to more patients with severe diabetes in the future. In order to achieve an effective fusion of islet transplantation and regenerative medicine, it may be of great importance to create radical innovation in each of the following three fields: Improvement of the subcutaneous islet transplantation method, Prevention or reduction of the side effects of immunosuppressive drugs, and Construction of insulin-producing cells.

【Objectives】 The purpose of this study is to clarify the dietary intakes of protein and salt in Japanese kidney transplant recipients (KTRs) over one year after the transplantation, and to identify nutritional issues in KTRs.

【Design】 Case-series study at a single center.

【Methods】 In 100 cases of non-diabetic adult KTRs at Japan Community Health Care Organization Sendai Hospital from 2005 to 2018, daily protein and salt intakes were determined by 24-hour urine collection, and their clinical and nutritional parameters were evaluated over one year after the transplantation. Using Dunnett’s test, the parameters at 3, 6, 9, and 12 months after the transplantation were compared to those at one month.

【Results】 At 6 months after the transplantation, the mean protein intake was increased significantly compared to that at one month. The mean salt intake over one year was 10.9 g/day, exceeding the dietary reference intake of salt (3-6 g/day). However, their BMI, body composition, nutritional and immunological parameters over one year after the transplantation were almost within the normal range, and the kidney functions were maintained stably in 72% of KTRs.

【Conclusion】 These results show that the nutritional and immunological parameters as well as kidney functions in KTRs were favorably maintained over one year after the transplantation. The salt intake of the KTRs should be managed in terms of the deterioration of kidney function and the appearance of circulatory diseases in the future.

A detailed survey for rituximab treatment for intestinal transplant was performed in 5 institutions where the intestinal transplant was carried out in Japan. Rituximab was used as a desensitization therapy for Donor Specific Antigen (DSA) positive recipients or as a treatment for antibody-mediated rejection. One case of each was reported from one institution. Rituximab has had certain effects such as preventing DSA from becoming negative and re-positive. As the number of re-transplanted cases increases, many DSA-positive cases are observed, and the use of rituximab seems to be essential. Furthermore, in intestinal transplantation, the incidence of chronic rejection is higher than in other solid organ transplants and rituximab may have a benefit on prognosis; therefore, rituximab is an essential drug for the intestinal transplant.

【Objective】 Transplantation is one the most successful areas of modern medicine. It is a life-saving medical modality and a symbol of human solidarity made possible by the generous act of organ donors and their families. The purpose of this review was to provide a comprehensive and updated global picture of the current practice.

【Data Sources and Data Extraction】 Cross-sectional data were obtained and extracted from academic, government, and international organization sources including Global Observatory on Donation and Transplantation, a World Health Organization collaboration (GODT/WHO), and literature review by MEDLINE/PubMed and Japan Medical Abstracts Society Web query.

【Study Selection】 Observational, Cross-sectional study.

【Results】 GODT/WHO reported 153,863 solid organ transplants and 40,608 deceased donors from 82 member states, which covered 74.3% of the global population for 2019. While western countries continue to lead with prominent scientific activity and ethical leadership, other regions and countries have emerged with significant progress. Geographical disparities in access, however, persist. Living donor transplantation continues to play an important role in many regions. Novel practice such as vascularized composite allograft transplantation, and transplantation of extremities, face, and uterus have emerged with successful outcomes. Implementation of effective allocation of resources including training and establishment of professional donor-procurement networks has been stressed.

【Conclusion】 Worldwide diffusion of transplant medicine continues. In the era of accelerating globalization and rapid technology transfer, continuing application of international ethical principles expressed in the Declaration of Istanbul is ever more important.