Humans ; Islets of Langerhans Transplantation

Islet transplantation had been suggested as a potential treatment modality for type I diabetes mellitus for the last two decades. The methods for the islet isolation and purification were developed. In 2000, the excellent clinical outcomes from the Edmonton group were reported. And various basic researches were performed for the elucidation of the mechanism of initial islet loss. Although the Edmonton protocol, which had initially raised hopes that all the technical and immunologic problems would be solved, recently revealed as a limited success within the selective cases and short-term follow-up, these inspirations led us to the subsequent clinical or basic research of islet transplantation. As a result, many clinical trials and studies have been attempted for the establishment of the optimal immune suppression regimen, the prevention from islet loss in the process of isolation, and the improvement of the intraportal engraftment. This article reviews the history and the recent progress and possible strategies for the clinical islet transplantation.
Diabetes Mellitus ; Hope ; Islets of Langerhans Transplantation*

Encapsulation of tissue has been an area of intense research with a myriad number of therapeutic applications as diverse as cancer, tissue regeneration, and diabetes. In the case of diabetes, transplantation of pancreatic islets of Langerhans containing insulin-producing beta cells has shown promise toward a cure. However, anti-rejection therapy that is needed to sustain the transplanted tissue has numerous adverse effects, and the islets might still be damaged by immune processes. Furthermore, the profound scarcity of healthy human donor organs restricts the availability of islets for transplant. Islet encapsulation allows the protection of this tissue without the use of toxic medications, while also expanding the donor pool to include animal sources. Before the widespread application of this therapy, there are still issues that need to be resolved. There are many materials that can be used, differing shapes and sizes of capsules, and varied sources of islets to name a few variables that need to be considered. In this review, the current options for capsule generation, past animal and human studies, and future directions in this area of research are discussed.
Animals ; Capsules ; Humans ; Immunosuppression ; Islets of Langerhans ; Islets of Langerhans Transplantation* ; Regeneration ; Tissue Donors ; Transplantation

Since the report of type 1 diabetes reversal in seven consecutive patients by the Edmonton protocol in 2000, pancreatic islet transplantation has been reappraised based on accumulated clinical evidence. Although initially expected to therapeutically target long-term insulin independence, islet transplantation is now indicated for more specific clinical benefits. With the long-awaited report of the first phase 3 clinical trial in 2016, allogeneic islet transplantation is now transitioning from an experimental to a proven therapy for type 1 diabetes with problematic hypoglycemia. Islet autotransplantation has already been therapeutically proven in chronic pancreatitis with severe abdominal pain refractory to conventional treatments, and it holds promise for preventing diabetes after partial pancreatectomy due to benign pancreatic tumors. Based on current evidence, this review focuses on islet transplantation as a realistic approach to treating diabetes.
Abdominal Pain ; Autografts ; Humans ; Hypoglycemia ; Insulin ; Islets of Langerhans ; Islets of Langerhans Transplantation* ; Pancreatectomy ; Pancreatitis, Chronic ; Transplantation, Autologous

Islet transplantation has been considered as an attractive procedure due to its simplicity, and because it can improve glycemic control in type 1 diabetic patient with hypoglycemic unawareness. In 2000, Shapiro et al. at the University of Alberta in Edmonton reported successful reversal of type 1 diabetes by pancreatic islet transplantation in seven patients with severe hypoglycemia, but no kidney disease. After the Edmonton milestone report, there has been an exponential increase in clinical islet transplantation activities. However, the revived enthusiasm regarding clinical islet transplantation after the landmark Edmonton trial has been decreased by the long-term results. The aim of this review is to summarize history, current status and the perspective of islet transplantation in patients with type 1 diabetes.
Alberta ; Humans ; Hypoglycemia ; Islets of Langerhans ; Islets of Langerhans Transplantation ; Kidney Diseases ; Transplants

INTRODUCTION: Islet cell transplantation is an attractive alternative to whole organ pancreas transplantation, because it is clearly the safer and simpler surgical procedure for recipients. PURPOSE: The authors intended to examine the functional outcome of islet autografting and the factors related to islet graft survival in mongrel dogs. METHODS: Eighteen adult mongrel dogs were used for the study of total pancreatectomy and islet autotransplantation. The harvested total pancreas was preserved in iced Hank's balanced salt solution (HBSS). The islets were properly isolated by a modified Recordi method. RESULTS: The median volume of the transplanted pancreatic islet tissue was 2.1 mL (range 0.7 to 5.0) and purity was 63% (range 10 to 95). Twelve dogs from the experimental group having undergone successful autografting of islets were followed for a minimum of 6 weeks. Three of the 12 dogs maintained insulin secretory function for 6 weeks and the other 7 dogs showed normal Kg values for 6 months following islet transplantation. In the remaining 2 cases, islet graft function was sustained for 1 year. The median required insulin dosage for maintenance of normal FPG was 0.7 U/kg per day (range 0 to 1.6). The insulin requirement correlated well with the IEq/ kg level (r=.90, P<.01). Dogs with >6,000 IEq/kg had a better chance of being insulin-independent. CONCLUSION: In this study, we confirmed that autotransplantation of islet cells on pancreatectomized dogs can render nearly normoglycemia, and islet transplantation dogs can be used as a model for the assessment of insulin secretory function.
Adult ; Animals ; Autografts* ; Dogs ; Graft Survival ; Humans ; Insulin ; Islets of Langerhans Transplantation ; Islets of Langerhans* ; Pancreas ; Pancreas Transplantation ; Pancreatectomy ; Transplantation, Autologous ; Transplants

Transplantation of the pancreas islet cell has been demonstrated to be able to cure for type I diabetes. It can offer not only discontinuing of insulin but also preventing of complications from diabetes. Islet cell transplantation has been very successful in small animals, but it is still unsuccessful in large animal, especially in non-human primate. Non-human primate trial has a value as a preclinical model prior to human application because of its close phylogenetic relationship to human. PURPOSE: The aim of this study is to develop the constant isolation method for obtaining sufficient number of islet in non-human primate pancreas to allow the human clinical islet transplantation more feasibly. METHODS: Ten pancreas were procured from cynomolgus (Macaca fasicularis) monkey. Islet isolation was done with the modified Ricordi's method using the new brand enzyme Liberase HI. Quantitaion of islet, viability staining insulin release without or with glucose stimulation, intracellular insulin content, DNA assay and in vivo transplantation into diabetic nude mice were done for quality control of islets. RESULTS: 2760 IEQ/pancreas gram with 91% of purity were able to be obtained by this isolation method using the new enzyme Liberase HI. These islets showed good quality of function, which demonstrated by in vitro standard assays. Euglycemia were achieved in 90% of streptozotocin induced diabetic nude mice by transplantation the purified islets (2,000 IEQ) into the subrenal space. CONCLUSION: Sufficient number of islets could be obtained from non-human primate through our method, and islets were able to respond glucose challenge and to eliminate the diabetes in streptozotocin induced diabetic nude mice. This implies we will be able to use this method as a preclinical model for human application for islet transplantation.
Animals ; DNA ; Glucose ; Haplorhini ; Humans* ; Insulin ; Islets of Langerhans ; Islets of Langerhans Transplantation ; Mice ; Mice, Nude ; Pancreas* ; Primates* ; Quality Control ; Streptozocin

PURPOSE: Cryopreservation of pancreas islet cells can facilitate the clinical islet transplantation by giving a means of storage of islets and immunomodulation on pancreatic islet preparations. METHODS: Pancreatic islets were isolated by standard technique using collagenase in rat. Cryopreservation was performed by using DMSO as a cryoprotectant after one day or 48 hr culture. Recovery rate, viability and insulin release in assay in vitro and vivo were checked under the various conditions, such as concentration of DMSO (1.5 M or 2.0 M), culture condition (1 day or 2 day), and taurine treatment. RESULTS: Percentage of recovery of cryopreserved islet was 56.8+/-10% after thawing. Viability was decreased from 97.2+/-1.1% before cryopreservation to 82.7+/-9.9% after thawing. Glucose stimulation index was reduced from 1.7+/-0.2 before cryopreservation to 1.2+/-0.8 after thawing. Nucleation method by metal rod showed better viability than control (no nucleation) or chamber nucleation method. Mean viability and glucose stimulation index was 81% and 1.5 in one day culture, and 84.2% and 1.2 in 2 day culture before cryopreservtion. Islet treated with taurine showed better insulin release and intracellular insulin content compared with non treated islets before and after cryopreservation. When 4000 IEQ (Islet Equivalent) of islets treated with taurine and non treated cryopreserved islets were transplanted into syngenic streptozotocin induced diabetic rat, all showed normoglycemia over 60 days. CONCLUSION: Cryopreservation of islets could give a tool of storage with preservation of islet secretion function. However pertinent effort to improve the recovery is needed in order to be used in the clinical islet transplantation.
Animals ; Collagenases ; Cryopreservation* ; Dimethyl Sulfoxide ; Glucose ; Immunomodulation ; Insulin ; Islets of Langerhans Transplantation ; Islets of Langerhans* ; Pancreas* ; Rats* ; Streptozocin ; Taurine

Impaired awareness of hypoglycemia has been found to be prevalent in 20% to 40% of people with type 1 diabetes. If a similar prevalence exists in Koreans with type 1 diabetes, at a minimum, thousands of people with type 1 diabetes suffer at least one unpredicted episode of severe hypoglycemia per year in Korea. For patients with problematic hypoglycemia, an evidence-based stepwise approach was suggested in 2015. The first step is structured education regarding multiple daily injections of an insulin analog, and the second step is adding a technological intervention, such as continuous subcutaneous insulin infusion or real-time continuous glucose monitoring. The next step is a sensor-augmented pump, preferably with a low glucose suspension feature or very frequent contact, and the final step is islet or pancreas transplantation. In Korea, however, none of these treatments are reimbursed by the National Health Insurance, and thus have not been widely implemented. The low prevalence of type 1 diabetes means that Korean physicians are relatively unfamiliar with the new technologies in this field. Therefore, the roles of new technologies and pancreas or islet transplantation in the treatment of problematic hypoglycemia need to be defined in the current clinical setting of Korea.
Education ; Glucose ; Humans ; Hypoglycemia* ; Insulin ; Islets of Langerhans Transplantation ; Korea* ; National Health Programs ; Pancreas ; Pancreas Transplantation ; Prevalence

OBJECTIVETo review the current status and progress on pig islet xenotransplantation.

DATA SOURCESData used in this review were mainly from English literature of Pubmed database. The search terms were "pig islet" and "xenotransplantation".

STUDY SELECTIONThe original articles and critical reviews selected were relevant to this review's theme.

RESULTSPigs are suggested to be an ideal candidate for obtaining available islet cells for transplantation. However, the potential clinical application of pig islet is still facing challenges including inadequate yield of high-quality functional islets and xenorejection of the transplants. The former can be overcome mainly by selection of a suitable pathogen-free source herd and the development of isolation and purification technology. While the feasibility of successful preclinical pig islet xenotranplantation provides insights in the possible mechanisms of xenogeneic immune recognition and rejection to overwhelm the latter. In addition, the achievement of long-term insulin independence in diabetic models by means of distinct islet products and novel immunotherapeutic strategies is promising.

CONCLUSIONSPig islet xenotransplantation is one of the prospective treatments to bridge the gap between the needs of transplantation in patients with diabetes and available islet cells. Nonetheless, further studies and efforts are needed to translate obtained findings into tangible applications.

Animals ; Graft Rejection ; immunology ; prevention & control ; Islets of Langerhans Transplantation ; immunology ; methods ; Swine ; Transplantation, Heterologous ; methods