Current Advancement of Islet Cell Transplantation in the Treatment of Diabetes Mellitus
Submission Deadline: September 30, 2018 (Open) Submit Now
Kenneth L. Brayman, MD, PhD, FACS
Professor of Surgery, Medicine, and Biomedical Engineering, Director of Kidney, Pancreas and Islet Transplant Programs, Director of Center for Cellular Therapy and Biologic Theraputics. Department of Surgery, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22908, USA
E-Mail: [email protected]
Research Interests: transplant immunosuppression, chronic allograft nephropathy, solid organ transplantation in patients with HIV, islet cell transplantation, transplantation tolerance, gene therapy and xenotransplantation
Title: Introduction of the Special Issue
Authors: Kenneth L. Brayman, Jose Oberholzer
Title: Pancreatic Allo Islet Transplantation: Update on Current Condition
Author: Rauf Shahbazov
Title: The Role of Auto Islet Transplantation in the Prevention of the Development of Diabetes Mellitus after Total Pancreatectomy
Author: Arash Nickholch
Title: Inflammatory Reaction in Islet Transplantation
Author: Mazhar Kanak
Title: Can An Islet be "Isolated" from the Immune System by Encapsulation?
Author: Meriegeng Qi
Title: Stem-Cell Therapy in Islet and Pancreas Transplantation
Author: Preeti Chhabra
Title: Role of Artificial Pancreas in islet Transplantation
Author: Kovatchev Boris
Title: Scaffolding for Diabetes: Reality or Myth.
Author: Yong Wang
Title: In Vitro and In vivo Imaging for Diabetes Research and Treatment
Author: Dongfeng Pan
Title: Islet Xenotransplantation for the Treatment of Type 1 Diabetes
Authors: Masayuki Shimoda MD PhD and Shinichi Matsumoto MD PhD, National Center for Global Health and Medicine, Japan
Allogeneic islet transplantation has been established to prevent severe hypoglycemia for unstable type 1 diabetic patients. Recent phase 3 clinical trial clearly demonstrated the benefit of allogeneic islet transplantation. Severe hypoglycemia is serious issue not only for type 1 diabetic patients but also type 2 diabetic patients especially aged patients. Considering the possible demands for such patients, donor shortage will be the serious issue. To solve this issue, islet xenotransplantation using porcine islets is a promising remedy. There are several advantages of porcine islets comparing with human islets including unlimited and on demand supplies, higher quality of islets from healthy donor, safer with designated pathogen free (DPF) donor pigs and possible gene modifications. Comparing ES and iPS derived islets, porcine islets have more profound clinical experiences with evidences of safety and efficacy since 1990s. In addition, promising outcomes were published using porcine islets to restore normoglycemia in the non-human primate diabetes models. One of the major concerns of islet xenotransplantation is zoonotic infections. To prevent this possible complication, using DPF status donor pigs, and monitoring porcine endogenous retrovirus (PERV) are key elements. In addition, compliance with regulatory rule is critically important to prevent spreading the zoonotic infections. Recently, international xenotransplantation association updated their consensus statements to promote islet xenotransplantation and it emphasized the importance of the regulatory compliance. In 2014, a clinical trial of encapsulated porcine islet xenotransplantation for the treatment of type 1 diabetes under comprehensive regulation was published. This study demonstrated the safety of islet xenotransplantation and some efficacy. Recently, it was published the encapsulated porcine islet xenotransplantation provided clinical benefit for type 1 diabetic patients. Encapsulated porcine islet xenotransplantation seems promising, and several groups have demonstrated improved capsules which may solve the fibrosis issue of capsules. CRISPR/CAS9 system makes the gene editing technology stable and easy. In fact, it was demonstrated that PERVs were completely eliminated with CRISPR technology. Human compatible pig will be made with this technology. Eventually, human pancreas will be created in pig body with blastocyst complementation technology. These aggressive scientific advances will bring islet xenotransplantation as a standard therapy for diabetic patients.
Title: Autoimmunity in Autologous Islet Transplantation
Authors: Khawla F. Ali1, Vicente T. San Martin1, Tyler Stevens2, Matthew Walsh2, Rita Bottino3, Betul Hatipoglu1
1. Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA;
2. Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA;
3. Institute for Cellular Therapeutics, Allegheny-Singer Research Institute, Pittsburgh, PA, USA;
Title: Intrapancreatic parenchymal cell transplantation (IPPCT) as a useful tool for study in cell-based therapy towards type I diabetes
Authors: Masahiro Sato, Emi Inada, Shingo Nakamura, Issei Saitoh
Title: Delayed clinically significant portal hypertension after TPIAT
Authors: Nicholas Lim, Gregory Beilman, Timothy Pruett
Title: Microbiology of High Risk Patients After Pancreatectomy and Autologous Islet Transplant
Authors: Daniel Robinson, Jennifer A Logue, William E Scott III, Minna Honkanen-Scott, Julian DeHaviland, Ahmad Abou-Saleh, Gabre M Hany, James AM Shaw, Derek M Manas, Richard M Charnley, Steven A White
Aim: Autologous islet transplantation (AIT) after pancreas resection has the potential to minimise glucose intolerance. Despite cell isolation being performed in a GMP facility some patients may be at an increased risk of infection. Two such cohorts could be those who have had previous drainage procedures (biliary or pancreatic) or those who have had significant pancreatic trauma. The risk of transmitting infection through the islet preparation in these types of patients is not well reported.
Methods: To date we have performed 8 islet autologous transplants (IAT) with 6 being in the relevant ‘high risk’ cohorts (previous pancreaticojejunostomy n=2, hepaticojejunostomy n=1 and pancreatic trauma n=3). Islets were isolated in a GMP HTA licensed facility. The pancreas is decontaminated with Fungizone, cephalosporin and a betadine wash prior to islet solation. We use BacT/ALERT SN culture bottles for detection of microbes in the pancreatic transport fluid (TF) and final washing (FW) steps. We also perform environmental monitoring by finger dabs, settle plates and from within the class II hoods. We also culture from the final islet preparation and perform a gram stain.
Results: Islet yields were significantly higher in the pancreatic trauma cohort (range 20,000 to 298,149 IEQ). All of those in this group (2 adults and 1 paediatric) remain insulin independent after more than 18 months follow up. In the drainage group 2 are C-peptide positive with the final patient still in the early recovery phase but insulin independent. One pancreatic trauma patient grew staph epidermidis in the TF but had no post-operative infections. Another required a re-laparotomy after developing an infected collection in the pancreatic bed which cultured staph aureus after no growth during the isolation process. One pancreatic drainage patient had contaminated TF and a FW but did not develop any systemic sepsis other than a minor wound infection. The previous hepaticojejunostomy patient had contaminated TF and FW concordant with a bile swab taken at the time of the procedure (E. coli and Enterococcus casseliflavus) but developed no infectious complications.
Conclusions: Patients perceived to be at ‘high risk’ of developing contaminated islet isolations can be safely transplanted without any infection risk. Culture of microbes during pancreas transportation and islet isolation do not always lead to systemic infective episodes after transplantation despite also undergoing major abdominal surgery.
Title: Nuclear Factor Erythroid-derived 2-like 2 (Nrf-2) Pathway is a Promising Target to Enhance Outcome of Pancreatic Islet Transplantation
Authors: Mahiro Kuroda, Nosratola D. Vaziri, Hirohito Ichii
Title: Targeting acute islet inflammation to preserve graft mass and long-term function
Authors: Carly Darden, Bashoo Naziruddin, Michael Lawrence
Title: Chemical Strategies for Improving Islet Transplant Outcomes
Authors: Jeremy M. Quintana, Michael A. Plunk, Jessica H. Kostyo, Alexandra L. Stinchcomb, Blair M. Robichaud, and Robert R. Kane
Title: Evolution of enzyme requirements for human islet isolation
Authors: Robert C. McCarthy, Michael L. Green, Francis E. Dwulet
Title: Where is Waldo? The best place to implant Islets
Authors: Greg J Beilman, Alexa Coughlan, Melena Bellin