Islet Transplantation Research Research Articles

Global scientific trends on the islet transplantation in the 21st century: A bibliometric and visualized analysis.

Islet transplantation (IT) has emerged as a significant research area for the treatment of diabetes mellitus and has witnessed a surge in scholarly attention. Despite its growing importance, there is a lack of bibliometric analyses that encapsulate the evolution and scientific underpinnings of this field. This study aims to fill this gap by conducting a comprehensive bibliometric analysis to delineate current research hotspots and forecast future trajectories within the IT domain with a particular focus on evidence-based medicine practices. This analysis scrutinized literature from January 1, 2000, to October 1, 2023, using the Web of Science Core Collection (WoSCC). Employing bibliometric tools such as VOSviewer, CiteSpace, and the R package "bibliometrix," we systematically evaluated the literature to uncover scientific trends and collaboration networks in IT research. The analysis revealed 8388 publications from 82 countries, predominantly the United States and China. However, global cross-institutional collaboration in IT research requires further strengthening. The number of IT-related publications has increased annually. Leading research institutions in this field include Harvard University, the University of Alberta, the University of Miami, and the University of Minnesota. "Transplantation" emerges as the most frequently cited journal in this area. Shapiro and Ricordi were the most prolific authors, with 126 and 121 publications, respectively. Shapiro also led to co-citations, totaling 4808. Key research focuses on IT sites and procedures as well as novel therapies in IT. Emerging research hotspots are identified by terms like "xenotransplantation," "apoptosis," "stem cells," "immunosuppression," and "microencapsulation." The findings underscore a mounting anticipation for future IT research, which is expected to delve deeper into evidence-based methodologies for IT sites, procedures, and novel therapeutic interventions. This shift toward evidence-based medicine underscores the field's commitment to enhancing the efficacy and safety of IT for diabetes treatment, signaling a promising direction for future investigations aimed at optimizing patient outcomes.

The streetlight effect--is there light at the end of the tunnel?

Autoimmune type 1 diabetes research and treatment are seemingly plagued with problems. Large and small, mostly well-thought out clinical studies and trials since the early 1980s have basically been negative. None of the treatments tested have reached clinical routine to replace current lifesaving insulin replacement therapy. A combination type of therapy to diminish the requirement for insulin is yet to be found. The chronic autoimmune disease at the time of clinical onset of type 1 diabetes has been the “winner” in all attempts made so far to stifle the disease process. The disease is also the “winner” over islet transplantation, a potential cure for diabetes. Islet transplantation research was drastically reduced after it was found that the so-called Edmonton protocol did not yield sustainable insulin independence despite short-term restoration of endogenous insulin production and glycemic stability (1). The Diabetes Control and Complications Trial (DCCT) study, well known to all, continues to underscore the importance of glucose control. The reduction in the risk of complications resulting from intensive therapy in patients with type 1 diabetes persisted at least for 4 years after the study was completed, despite increasing hyperglycemia (2). Notwithstanding progress in the overall diabetes management, we were all recently reminded of the fact that type 1 diabetes remains a deadly disease (3). Although mortality was the highest in patients with poorly controlled diabetes, it was reported that patients with type 1 diabetes with A1C of 6.9% or lower had a risk of death from any cause that was twice as high as the risk for matched control subjects (3). Against this background of an uphill battle, the current issue of Diabetes contains a Perspective by Battaglia and Atkinson entitled “The Streetlight Effect in Type 1 Diabetes” (4). In their Perspective, the authors put forward several remedies to …

Pancreatic islet transplantation: from dogs to humans and back again.

Pancreatic islet transplantation is a cell-based therapy that provides a potential cure for type 1 diabetes mellitus. After the introduction of an automated method for islet isolation and steroid-free immunosuppressive protocols, reversal of diabetes by islet transplantation is now performed at major human medical centers around the world. Despite extensive use of animal models in islet transplantation research, practical concerns have slowed the introduction of the technique into clinical veterinary practice and only a small number of studies have reported results of transplantation in dogs with spontaneously occurring diabetes mellitus; however, recent advances in islet isolation and encapsulation may make it possible to perform islet transplantation without immunosuppression in companion animals. This review summarizes experimental and clinical studies of pancreatic islet transplantation in dogs, including future directions for cell therapy in animals with naturally occurring disease.

Pancreas and islet cell transplantation in diabetes

The following review of the field of whole organ pancreas and islet cell transplantation for type 1 diabetes mellitus is timely and relevant, since new findings and outcomes in both fields have emerged in the recent past. Research in the field of whole organ pancreas transplantation is characterized by small advances in knowledge in an established, but not widely used procedure. For islet transplantation, the field is evolving more rapidly. Disappointing clinical trial results, however, have hampered enthusiasm for this procedure. Islet transplantation research recently has focused on delineating possible causes of failure to achieve or sustain insulin independence and innovations to address both this failure and the current shortage of islets for clinical transplantation. Pancreas transplantation research is less innovative at this point, focusing mainly on optimizing clinical results. These published findings suggest that at the present time, clinical application of islet transplantation should be limited to clinical trials, focusing on techniques to enhance islet engraftment and survival. Whole organ pancreas transplantation remains the preferable transplant option for the type one diabetic patient.

7th Annual Meeting of the Egyptian Society of Pancreatic Islet Transplantation Research for Diabetic Patients

7th Annual Meeting of the Egyptian Society of Pancreatic Islet Transplantation Research for Diabetic Patients

Bioluminescence Imaging of Pancreatic Islet Transplants

Bioluminescence imaging (BLI) modalities have been developed, refined, and used broadly in the study of small animal models of human biology and disease. Here, we review the importance of developing an in vivo imaging modality for real-time monitoring islets post transplantation. In order to advance our understanding of the pathophysiology and immunobiology of islet transplantation as they occur in living animals, islet grafts tagged with lightemitting luciferase can be implanted in a mouse islet transplantation model and assessed using in vivo BLI. Some of the preliminary data, considerations of using the system, and future applications of BLI in the field of islet transplantation research are discussed. Keywords: bioluminescence, imaging, islet transplantation, in vivo, transgenic mice, luciferase, luciferin

A simple and cost-effective method for the isolation of islets from nonhuman primates.

Recent advances in islet cell transplantation have led to insulin independence in a majority of islet transplant recipients. However, there exists a need to overcome the shortage of donor tissue and the necessity for life-long immunosuppression. Preclinical studies in large animal models are necessary to evaluate the safety and efficacy of alternative approaches for clinical islet transplantation. The nonhuman primate serves as an appropriate animal model for such investigations; however, a major impediment in performing such preclinical research has been the difficulty in isolating islets of sufficient quantity and quality. The current study describes a simple and cost-effective method to isolate nonhuman primate islets to support preclinical islet transplantation research. The results of islet isolations from 54 cynomolgus monkeys and 4 baboons are reported. The pancreas was infused with Liberase HI and subjected to static digestion. The digested tissue was shaken, filtered through a mesh screen, applied to a discontinuous gradient, and centrifuged in much the same manner as with conventional rodent islet isolations. Islets were collected from the two interfaces, washed, and transplanted. Following purification, cynomolgus monkey islet isolation yields were 50,100 +/- 3120 IE total or 8760 +/- 420 IE/g pancreas with the percent purity and viability of 90.8 +/- 0.9 and 90.7 +/- 0.7, respectively. Total insulin content of the isolated islets was 405 +/- 53 microg insulin with DNA content being and 976 +/- 117 microg DNA, corresponding to a ratio of 0.57 microg insulin/microg DNA. STZ-induced diabetes was reversed in both mouse and nonhuman primate recipients, which possessed significant levels of c-peptide following transplantation and well-granulated islet grafts. The technique yields sufficient numbers of pure and viable islets to support preclinical research to develop improved strategies to prevent the immune destruction of the transplanted islet graft.

Successful Cryopreservation of Fetal Porcine Proislets

This study reports the cryopreservation of purified fetal pig proislets (FPP) which were isolated by a culture technique. The FPP were equilibrated with 2 M dimethyl sulfoxide (Me 2SO), cooled at a rate of 0.25°C/min to -40°C, transferred to liquid nitrogen ( - 196°C), stored for 2 h to 2 months at - 196°C, and thawed in a 37°C water bath. The morphology of frozen-thawed FPP was similar to that of noncryopreserved FPP. One hundred percent recovery of response capacity was achieved when tested with 16.7 m M glucose plus 10 m M theophylline. We have recently shown that streptozotocin is not toxic to FPP. Accordingly, we transplanted a standardized dose (10-15 mg/mouse) of either cultured or frozen-thawed FPP beneath the renal capsule of nude mice. Three to four weeks later the recipients of the FPP were rendered diabetic by iv streptozotocin. All of the mice transplanted with cultured FPP and seven of eight mice receiving cryopreserved FPP achieved normoglycemia, 74.8 ± 32.9 and 54.7 ± 8.1 days ( P > 0.05) after transplantation. An intraperitoneal glucose tolerance test in the mice of both groups showed a flatter response to glucose compared to those of normal controls. Grafts removed from the mice with normoglycemia for > 3 weeks, in both groups, had the capacity to secrete insulin in response to 16.7 m M glucose alone and 16.7 m M glucose plus 10 m M theophylline during in vitro perifusion. Histological examination revealed that the extent of differentiation and development, in vivo of cryopreserved FPP was comparable with that of cultured FPP. These data indicate that cryopreservation, with the protocol used here, is successful in maintaining functional viability of frozen-thawed FPP. This study is valuable for clinical islet transplantation research.