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Shinichi Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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No PERV transmission during a clinical trial of pig Islet Cell Transplantation
Virus research, 2016Co-Authors: Vladimir A. Morozov, Shinichi Matsumoto, Shaun Wynyard, Adrian Abalovich, Joachim Denner, Robert B. ElliottAbstract:XenoTransplantation of pig Islet Cells is a promising alternative for the treatment of diabetes with insulin and may help to prevent numerous late complications such as blindness and amputation. First encouraging results using porcine Islets have been reported in preclinical animal models as well in the first clinical trial in New Zealand. The goal of this manuscript is to examine the biological safety of a second trial performed in Argentina, specifically in regards to the transmission of porcine endogenous retroviruses (PERVs) using improved detection methods As in the first trial encapsulated Islet Cells from the well-characterised Auckland Island pigs were used. The animals were not genetically modified. The Islet Cells were transplanted in eight human recipients using a modified clinical protocol. Sera taken at different time points after Transplantation (up to 55 weeks) were screened for the presence of antibodies against PERV proteins by Western blot analysis using viral antigens from highly purified virus particles. Positive sera obtained by immunization with recombinant PERV proteins were used as control sera. In none of the patients antibodies against PERV were detected, indicating the absence of infection. In parallel at different time points (up to 113 weeks) white blood Cells (WBC) have been tested for PERV DNA, and WBC and plasma for PERV RNA by real-time RT-PCR. All tests were negative. In addition, using primers detecting pig mitochondrial cytochrome oxidase (COX) gene, patients were screened for microchimerism. In summary, the data are further evidence for the safety of pig Islet Cell Transplantation.
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Islet Cell Transplantation: New Techniques for an Old Disease
Technological Advances in Surgery Trauma and Critical Care, 2015Co-Authors: Shinichi Matsumoto, Masayuki ShimodaAbstract:Islet Cell Transplantation is a promising treatment towards curing diabetes. Recently, the clinical outcomes have improved and this treatment has become a standard therapy for type 1 diabetic patients in several countries. Technical improvements of Islet isolation include new pancreas preservation methods, new collagenase enzymes, and purification methods. In addition, immunosuppression protocols, especially T Cell depletion induction and anti-inflammation strategies at the time of Islet Transplantation, have impact on the clinical outcomes. Several institutes have demonstrated that it is possible to achieve insulin independence after single-donor Islet Transplantation. This is a breakthrough since one of the major concerns of Islet Cell Transplantation is inefficiency which exaggerates the donor shortage. Considering the huge numbers of diabetic patients, it is necessary to explore the Cell source other than human donor pancreas. Islet Transplantation using porcine Islets is a promising treatment to overcome the donor shortage and in fact, clinical trials of neonatal porcine Islet Transplantations have been conducted. Stem-Cell-derived insulin-producing Cells have been created and the clinical trials of such Cells might happen once current hurdles will be overcome. With advanced Islet Transplantation, it is desirable that diabetes would be converted from non-curable disease to curable disease.
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safety and tolerability of the t Cell depletion protocol coupled with anakinra and etanercept for clinical Islet Cell Transplantation
Clinical Transplantation, 2012Co-Authors: Morihito Takita, Shinichi Matsumoto, Masayuki Shimoda, Nicholas Onaca, Daisuke Chujo, Takeshi Itoh, Jeffrey A Sorelle, Kerri Purcell, Bashoo NaziruddinAbstract:Background Islet Cell Transplantation (ICT) is a promising approach to cure patients with type 1 diabetes. We have implemented a new immunosuppression protocol with antithymoglobulin plus anti-inflammatory agents of anakinra and eternacept for induction and tacrolimus plus mycophenolate mofetil for maintenance [T-Cell depletion with anti-inflammatory (TCD-AI) protocol], resulting in successful single-donor ICT. Methods Eight Islet recipients with type 1 diabetes reported adverse events (AEs) monthly. AEs were compared between three groups: first infusion with the TCD-AI protocol (TCD-AI-1st) and first and second infusion with the Edmonton-type protocol (Edmonton-1st and Edmonton-2nd). Results The incidence of symptomatic AEs within the initial three months in the TCD-AI-1st group was less than in the Edmonton-1st and Edmonton-2nd groups, with a marginally significant difference (mean ± SE: 5.5 ± 0.3, 7.5 ± 0.5, and 8.3 ± 1.3, respectively; p = 0.07). A significant reduction in liver enzyme elevation after ICT was found in the TCD-AI-1st group compared with the Edmonton-1st and Edmonton-2nd groups (p < 0.05). Because of AEs, all patients in the Edmonton protocol eventually converted to the TCD-AI protocol, whereas all patients tolerated the TCD-AI protocol. Conclusions TCD-AI protocol can be tolerated for successful ICT, although this study includes small cohort, and large population trial should be taken.
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Clinical allogeneic and autologous Islet Cell Transplantation: update.
Diabetes & metabolism journal, 2011Co-Authors: Shinichi MatsumotoAbstract:Islet Cell Transplantation is categorized as a β-Cell replacement therapy for diabetic patients who lack the ability to secrete insulin. Allogeneic Islet Cell Transplantation is for the treatment of type 1 diabetes, and autologous Islet Cell Transplantation is for the prevention of surgical diabetes after a total pancreatectomy. The issues of allogeneic Islet Cell Transplantation include poor efficacy of Islet isolation, the need for multiple donor pancreata, difficulty maintaining insulin independence and undesirable side effects of immunosuppressive drugs. Those issues have been solved step by step and allogeneic Islet Cell Transplantation is almost ready to be the standard therapy. The donor shortage will be the next issue and marginal and/or living donor Islet Cell Transplantation might alleviate the issue. Xeno-Islet Cell Transplantation, β-Cell regeneration from human stem Cells and gene induction of the naive pancreas represent the next generation of β-Cell replacement therapy. Autologous Islet Cell Transplantation after total pancreatectomy for the treatment of chronic pancreatitis with severe abdominal pain is the standard therapy, even though only limited centers are able to perform this treatment. Remote center autologous Islet Cell Transplantation is an attractive option for hospitals performing total pancreatectomies without the proper Islet isolation facilities.
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Secretory unit of Islet transplant objects (SUITO) index can predict severity of hypoglycemic episodes in clinical Islet Cell Transplantation.
Cell transplantation, 2011Co-Authors: Morihito Takita, Shinichi Matsumoto, Masayuki Shimoda, Nicholas Onaca, Hirofumi Noguchi, Daisuke Chujo, Takeshi Itoh, Koji Sugimoto, Huanying Qin, Bashoo NaziruddinAbstract:One endpoint of clinical Islet Cell Transplantation for type 1 diabetic patients is the elimination or reduction of hypoglycemia. We previously developed a simple tool to evaluate Islet graft function: the secretory unit of Islet transplant objects (SUITO) index. The aim of this study is to clarify the association between the SUITO index and hypoglycemic episodes. Data from 310 clinical evaluations of 11 Islet recipients were included in this study. Fasting plasma C-peptide and glucose levels were measured at every evaluation. The SUITO index was calculated according to the following formula: 1500 × C-peptide level (ng/ml)/[blood glucose level (mg/dl) - 63]. The number of hypoglycemic events (
Jose Oberholzer - One of the best experts on this subject based on the ideXlab platform.
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Concerns and hopes of patients with type 1 diabetes prior to Islet Cell Transplantation: A content analysis.
Journal of diabetes and its complications, 2018Co-Authors: Queena F. Luu, Jose Oberholzer, Rebecca S. Monson, Celine J. Villareal, Cynthia Fritschi, Kirstie K. DanielsonAbstract:Abstract Aims Islet Cell Transplantation can functionally cure type 1 diabetes complicated by hypoglycemia unawareness (HU), but requires immunosuppression. This study identified the lived experiences and risk/benefit considerations of patients pre-transplant. Methods Content analysis identified themes from four open-ended questions pre-transplant in an Islet transplant clinical trial. The sample included 23 (19 female) patients, with a mean age = 48.3 and diabetes duration = 29.3 years. Results Lack of control due to diabetes and HU was the overarching theme pre-transplant. Four sub-themes were also identified: fear of hypoglycemia, diabetes-related complications, hopes/expectations after transplant, and transplant outcomes. Patients expressed fear of HU and long-term complications pre-transplant, and hoped Islet transplant would improve diabetes management. Patients further emphasized anxiety over burdening others, and hopes of advancing research. In addition, other patients emphasized frustrations regarding the impact of HU on themselves, such as the inability to perform activities of daily living. Many patients were primarily worried about immunosuppressive side effects rather than Islet transplant success. Conclusions Patients viewed Islet Transplantation as a means to gain autonomy and control over their lives. They desired reduced anxiety associated with HU, despite concerns over immunosuppressive side-effects. These findings need confirmation, but may help to further improve patient education and patient-provider communication.
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Coronary artery calcium may stabilize following Islet Cell Transplantation in patients with type 1 diabetes.
Clinical transplantation, 2017Co-Authors: Jessica M. Madrigal, Betül Hatipoğlu, Jose Oberholzer, Rebecca S. Monson, George T. Kondos, Krista A. Varady, Kirstie K. DanielsonAbstract:Islet Cell Transplantation can functionally cure type 1 diabetes, and also improve carotid-intima media thickness. This study provides a preliminary description of changes in coronary artery calcium following Islet Transplantation, and associated factors. Coronary artery calcium was measured in 14 patients with type 1 diabetes (11 had measures both pre- and post-transplant [mean 2.3 years]) in the University of Illinois at Chicago's clinical trial. Multivariable mixed-effects linear regression of repeated measures was used to quantify calcium change, and determine if this change was longitudinally associated with risk/protective factors. Thirteen of the patients were female, with mean baseline age, diabetes duration, and BMI of 47.6 and 28.7 years and 23.1, respectively. Over half (57%) had detectable coronary artery calcium pre-transplant. Minimal change (0.39 mm3/year, p=0.02) occurred in coronary artery calcium levels pre- to post-transplant. No patient met criteria for calcium progression. Coronary artery calcium was positively associated with total and small VLDL particles (p≤0.02), statin dose (p=0.02), and urine albumin-to-creatinine ratio (p=0.04); and negatively associated with free fatty acids (p=0.03), total HDL (p=0.03), large HDL particles (p=0.005), and tacrolimus dose (p=0.02). Islet transplant may stabilize coronary artery calcium, with optimal management of lipids and kidney function remaining key therapeutic targets. [NCT00679041] This article is protected by copyright. All rights reserved.
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Percutaneous Pancreatic Islet Cell Transplantation
Endovascular Interventions, 2013Co-Authors: Felix Y. Yap, Jose Oberholzer, Raquel Garcia-roca, Ron C. GabaAbstract:Percutaneous pancreatic Islet Cell Transplantation is a promising Cellular-based therapy for type 1 diabetes mellitus (DM). This procedure involves portal venous injection of Islet Cells and affords 1-year insulin independence in up to 70 % of recipients. While transplant surgeons represent the historical drivers of Islet therapy, requirement for image-guidance and transcatheter techniques has fostered collaboration with interventional radiologists (IRs), who play a significant role in clinical performance of Islet Transplantation. The following case reviews the procedural elements of Islet Cell Transplantation with stepwise illustration of the interventional radiologic technique. The logistics involved in establishing and developing an Islet Cell Transplantation program and the technical aspects of pancreatic organ harvest and Islet Cell isolation and preparation are beyond the scope of this chapter and will not be presented.
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pancreatic Islet Cell Transplantation an update for interventional radiologists
Journal of Vascular and Interventional Radiology, 2012Co-Authors: Ron C. Gaba, Raquel Garciaroca, Jose OberholzerAbstract:Abstract Pancreatic Islet Cell Transplantation is a promising Cellular-based therapy for type 1 diabetes mellitus. This procedure involves portal venous injection of Islet Cells and affords 1-year insulin independence in as many as 80% of recipients. Although transplant surgeons represent historical drivers of Islet therapy, requirement for image guidance and transcatheter techniques has fostered collaboration with interventional radiologists, who are positioned to play a significant role in clinical performance of Islet Transplantation and in basic science research in this field. This review article aims to familiarize interventional radiologists with Islet Cell Transplantation patient selection, procedure technique, clinical outcomes, and future clinical and research avenues.
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A Case of Pancreatic Islet Cell Transplantation in a Patient with Situs Ambiguous: Anatomical and Radiological Considerations
Seminars in Interventional Radiology, 2007Co-Authors: Rajesh P. Shah, Derek L. West, Joan Martellotto, Betül Hatipoğlu, Jose Oberholzer, Charles A. OwensAbstract:Pancreatic Islet Cell Transplantation is an evolving treatment of severe, refractory type 1 diabetes that has been gaining more use, particularly after one year rates of insulin independence post-Transplantation were found to approach 80% under the Edmonton protocol. Islet Cell Transplantation involves percutaneous delivery of harvested allogeneic β Cells into the portal venous circulation for implantation into the liver. We present the case of a 35-year-old woman with type 1 diabetes and situs ambiguous with left isomerism and resultant variant anatomy of her portal venous anatomy who underwent Islet Cell Transplantation, which, to our knowledge, has not been previously reported.
Bart O. Roep - One of the best experts on this subject based on the ideXlab platform.
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Serum cytokines as biomarkers in Islet Cell Transplantation for type 1 diabetes
PloS one, 2016Co-Authors: Cornelis R. Van Der Torren, Annemarie A. Verrijn Stuart, Dahae Lee, Jenny Meerding, Ursule Van De Velde, Daniel Pipeleers, Pieter Gillard, Bart Keymeulen, Wilco De Jager, Bart O. RoepAbstract:BACKGROUND: Islet Cell Transplantation holds a potential cure for type 1 diabetes, but many Islet recipients do not reach long-lasting insulin independence. In this exploratory study, we investigated whether serum cytokines, chemokines and adipokines are associated with the clinical outcome of Islet Transplantation. METHODS: Thirteen Islet transplant patients were selected on basis of good graft function (reaching insulin independence) or insufficient engraftment (insulin requiring) from our cohort receiving standardized grafts and immune suppressive therapy. Patients reaching insulin independence were divided in those with continued (>12 months) versus transient (
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serum cytokines as biomarkers in Islet Cell Transplantation for type 1 diabetes
PLOS ONE, 2016Co-Authors: Cornelis R. Van Der Torren, Dahae Lee, Jenny Meerding, Ursule Van De Velde, Daniel Pipeleers, Pieter Gillard, Bart Keymeulen, Wilco De Jager, Annemarie Verrijn A Stuart, Bart O. RoepAbstract:BACKGROUND: Islet Cell Transplantation holds a potential cure for type 1 diabetes, but many Islet recipients do not reach long-lasting insulin independence. In this exploratory study, we investigated whether serum cytokines, chemokines and adipokines are associated with the clinical outcome of Islet Transplantation. METHODS: Thirteen Islet transplant patients were selected on basis of good graft function (reaching insulin independence) or insufficient engraftment (insulin requiring) from our cohort receiving standardized grafts and immune suppressive therapy. Patients reaching insulin independence were divided in those with continued (>12 months) versus transient (<6 months) insulin independence. A panel of 94 proteins including cytokines and adipokines was measured in sera taken before and at one year after Transplantation using a validated multiplex immunoassay platform. RESULTS: Ninety serum proteins were detectable in concentrations varying markedly among patients at either time point. Thirteen markers changed after Transplantation, while another seven markers changed in a clinical subpopulation. All other markers remained unaffected after Transplantation under generalized immunosuppression. Patterns of cytokines could distinguish good graft function from insufficient function including IFN-α, LIF, SCF and IL-1RII before and after Transplantation, by IL-16, CCL3, BDNF and M-CSF only before and by IL-22, IL-33, KIM-1, S100A12 and sCD14 after Transplantation. Three other proteins (Leptin, Cathepsin L and S100A12) associated with loss of temporary graft function before or after Transplantation. CONCLUSIONS: Distinct cytokine signatures could be identified in serum that predict or associate with clinical outcome. These serum markers may help guiding patient selection and choice of immunotherapy, or act as novel drug targets in Islet Transplantation.
Marlon F. Levy - One of the best experts on this subject based on the ideXlab platform.
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pancreatic β Cell derived ip 10 cxcl10 Isletokine mediates early loss of graft function in Islet Cell Transplantation
Diabetes, 2017Co-Authors: Gumpei Yoshimatsu, Faisal Kunnathodi, Prathab Balaji Saravanan, Rauf Shahbazov, Charles A Chang, Carly M Darden, Sandra Zurawski, Gulbahar Boyuk, Mazhar A Kanak, Marlon F. LevyAbstract:Pancreatic Islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these “Isletokines” in health and disease is largely unknown. We observed that Islets release multiple inflammatory mediators in patients undergoing Islet transplants within hours of infusion. The proinflammatory cytokine interferon-γ–induced protein 10 (IP-10/CXCL10) was among the highest released, and high levels correlated with poor Islet transplant outcomes. Transgenic mouse studies confirmed that donor Islet–specific expression of IP-10 contributed to Islet inflammation and loss of β-Cell function in Islet grafts. The effects of Islet-derived IP-10 could be blocked by treatment of donor Islets and recipient mice with anti–IP-10 neutralizing monoclonal antibody. In vitro studies showed induction of the IP-10 gene was mediated by calcineurin-dependent NFAT signaling in pancreatic β-Cells in response to oxidative or inflammatory stress. Sustained association of NFAT and p300 histone acetyltransferase with the IP-10 gene required p38 and c-Jun N-terminal kinase mitogen-activated protein kinase (MAPK) activity, which differentially regulated IP-10 expression and subsequent protein release. Overall, these findings elucidate an NFAT-MAPK signaling paradigm for induction of Isletokine expression in β-Cells and reveal IP-10 as a primary therapeutic target to prevent β-Cell–induced inflammatory loss of graft function after Islet Cell Transplantation.
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Islet Cell Transplantation for the treatment of type 1 diabetes in the USA
Journal of Hepato-Biliary-Pancreatic Surgery, 2008Co-Authors: Tetsuya Ikemoto, Masayuki Shimoda, Nicholas Onaca, Marlon F. Levy, Bashoo Naziruddin, Hirofumi Noguchi, Andrew Jackson, Yoshiko Tamura, Yasutaka Fujita, Shinichi MatsumotoAbstract:Islet Cell Transplantation (ICTx) is one of the most effective treatments for type 1 diabetes and is less invasive compared to whole organ Transplantation. The US has been the leader in the research and clinical applications of ICTx for the last 40 years. ICTx requires complex procedures, including pancreas procurement and preservation; pancreas digestion; Islet purification; and Transplantation. Even with the dramatic progresses in each of the procedures listed above, there are still challenges to make ICTx the standard therapy. These challenges are: (1) obtaining enough Islets from a single donor and (2) preventing graft loss due to allogenic rejection and recurrence of autoimmune Islet destruction. A new preservation strategy for pancreata and pancreatic ducts using ET-Kyoto solution as well as a new Islet purification method using iodixanol has substantially improved Islet yields. Continuous research to improve the efficacy of Islet isolation will solve the issue of obtaining enough Islets from a single donor. Immunological tolerance is an ideal solution for the issue of rejection and autoimmune recurrence and a regulatory T Cell strategy seems promising. Moreover, the SUITO index is a simple and powerful tool to assess engrafted Islet mass and is, therefore, useful for evaluating the efficacy of new immunosuppressant strategies. Once ICTx becomes a standard treatment, the donor shortage will become the next challenge. Marginal or living donor Islet Transplantations could help alleviate this issue; however, bio-artificial Islet Transplantation with animal Islets could be the ultimate solution.
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Pancreatic Islet Cell Transplantation: update and new developments.
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2007Co-Authors: Nicholas Onaca, Shinichi Matsumoto, Goran B. Klintmalm, Bashoo Naziruddin, Hirofumi Noguchi, Marlon F. LevyAbstract:Pancreatic Islet Cell Transplantation is a treatment alternative for patients with type 1 diabetes who experience hypoglycemic unawareness despite maximal care. The good results obtained by the group from Edmonton and other centers, with 80% insulin independence at 1 year posttransplant, are not sustainable over time, with 5-year insulin independence achieved in only 10% of patients. However, persistent graft function, even without insulin independence, results in improved glucose control and avoidance of hypoglycemic events. Changes in organ preservation, Islet processing technique, and immunosuppression regimens can result in improvement of results in the future. Islet autoTransplantation is an option for patients who undergo total pancreatectomy for chronic pancreatitis with debilitating pain, in which reinfusion of the Islets from the resected pancreas can result in avoidance of postsurgical diabetes or enhanced glucose control.
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Pancreatic Islet Cell Transplantation: a treatment strategy for type I diabetes mellitus.
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2004Co-Authors: Nicholas Onaca, Goran B. Klintmalm, Marlon F. LevyAbstract:Type I diabetes mellitus continues to be a serious disease with long-term morbidity from complications of the disease, despite better knowledge of physiology and better patient care. Pancreatic Islet Cell Transplantation, still experimental, is gaining acceptance as a treatment strategy for individuals with type 1 diabetes who have poor glucose control and frequent hypoglycemic episodes despite maximal care. The procedure can improve glucose control, avoiding further hypoglycemic episodes, and can achieve insulin-independence at the expense of immunosuppression treatment. Islet Cell Transplantation does not correct all the metabolic abnormalities seen in type 1 diabetes, and glucose tolerance can remain abnormal. The dietary management of the patients still needs to be defined. Further research is focused at improvement in Islet isolation and the refinement of immunosuppression strategies aiming toward immune tolerance, bringing hope for a cure of diabetes.
Nicholas Onaca - One of the best experts on this subject based on the ideXlab platform.
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safety and tolerability of the t Cell depletion protocol coupled with anakinra and etanercept for clinical Islet Cell Transplantation
Clinical Transplantation, 2012Co-Authors: Morihito Takita, Shinichi Matsumoto, Masayuki Shimoda, Nicholas Onaca, Daisuke Chujo, Takeshi Itoh, Jeffrey A Sorelle, Kerri Purcell, Bashoo NaziruddinAbstract:Background Islet Cell Transplantation (ICT) is a promising approach to cure patients with type 1 diabetes. We have implemented a new immunosuppression protocol with antithymoglobulin plus anti-inflammatory agents of anakinra and eternacept for induction and tacrolimus plus mycophenolate mofetil for maintenance [T-Cell depletion with anti-inflammatory (TCD-AI) protocol], resulting in successful single-donor ICT. Methods Eight Islet recipients with type 1 diabetes reported adverse events (AEs) monthly. AEs were compared between three groups: first infusion with the TCD-AI protocol (TCD-AI-1st) and first and second infusion with the Edmonton-type protocol (Edmonton-1st and Edmonton-2nd). Results The incidence of symptomatic AEs within the initial three months in the TCD-AI-1st group was less than in the Edmonton-1st and Edmonton-2nd groups, with a marginally significant difference (mean ± SE: 5.5 ± 0.3, 7.5 ± 0.5, and 8.3 ± 1.3, respectively; p = 0.07). A significant reduction in liver enzyme elevation after ICT was found in the TCD-AI-1st group compared with the Edmonton-1st and Edmonton-2nd groups (p < 0.05). Because of AEs, all patients in the Edmonton protocol eventually converted to the TCD-AI protocol, whereas all patients tolerated the TCD-AI protocol. Conclusions TCD-AI protocol can be tolerated for successful ICT, although this study includes small cohort, and large population trial should be taken.
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Secretory unit of Islet transplant objects (SUITO) index can predict severity of hypoglycemic episodes in clinical Islet Cell Transplantation.
Cell transplantation, 2011Co-Authors: Morihito Takita, Shinichi Matsumoto, Masayuki Shimoda, Nicholas Onaca, Hirofumi Noguchi, Daisuke Chujo, Takeshi Itoh, Koji Sugimoto, Huanying Qin, Bashoo NaziruddinAbstract:One endpoint of clinical Islet Cell Transplantation for type 1 diabetic patients is the elimination or reduction of hypoglycemia. We previously developed a simple tool to evaluate Islet graft function: the secretory unit of Islet transplant objects (SUITO) index. The aim of this study is to clarify the association between the SUITO index and hypoglycemic episodes. Data from 310 clinical evaluations of 11 Islet recipients were included in this study. Fasting plasma C-peptide and glucose levels were measured at every evaluation. The SUITO index was calculated according to the following formula: 1500 × C-peptide level (ng/ml)/[blood glucose level (mg/dl) - 63]. The number of hypoglycemic events (
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Variables associated with Islet yield in autologous Islet Cell Transplantation for chronic pancreatitis.
Proceedings (Baylor University. Medical Center), 2010Co-Authors: Morihito Takita, Shinichi Matsumoto, Masayuki Shimoda, Nicholas Onaca, Bashoo Naziruddin, Hirofumi Noguchi, Daisuke Chujo, Takeshi Itoh, Koji Sugimoto, Jeffrey P. LamontAbstract:Chronic pancreatitis (CP) is a progressive inflammatory disease that destroys not only pancreatic acini but also Islets in its late stage (1, 2). Episodes of severe abdominal pain are usually present in the natural course of CP, where both exocrine and endocrine function is also lost. Efforts such as decreasing smoking and alcohol use, taking oral pancreatic-enzyme supplements, and receiving endoscopic therapies such as sphincterotomy and stent placement are usually effective in managing pain and inhibiting disease progression; however, some patients have refractory or recurrent disease. Surgical options for CP treatment include drainage procedures such as the Puestow procedure and resections such as pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy. These are effective in reducing severe abdominal pain but may not maintain endocrine function (3, 4). Total or near total pancreatectomy (TP) followed by autologous Islet Cell Transplantation (AIT) was developed for both pain management and maintenance of pancreatic endocrine function, especially glycemic control (5–7). A few institutes in the world have performed TP with AIT, since AIT requires special techniques for Islet Cell processing, and the effectiveness of this procedure has been reported (5). We started allogeneic Islet Cell Transplantation for patients with type 1 diabetes mellitus in 2005 (8, 9) and initiated AIT for CP in November 2006 at Baylor University Medical Center. Novel methods for pancreas procurement and preservation, which were originally developed for the processing of pancreatic Islets from non–heart-beating donors in Japan (10, 11), were introduced in December 2007 to maximize the outcome of Islet isolation. This retrospective study of our experience with TP with AIT aimed to investigate variables associated with increased Islet yield.
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Islet Cell Transplantation for the treatment of type 1 diabetes in the USA
Journal of Hepato-Biliary-Pancreatic Surgery, 2008Co-Authors: Tetsuya Ikemoto, Masayuki Shimoda, Nicholas Onaca, Marlon F. Levy, Bashoo Naziruddin, Hirofumi Noguchi, Andrew Jackson, Yoshiko Tamura, Yasutaka Fujita, Shinichi MatsumotoAbstract:Islet Cell Transplantation (ICTx) is one of the most effective treatments for type 1 diabetes and is less invasive compared to whole organ Transplantation. The US has been the leader in the research and clinical applications of ICTx for the last 40 years. ICTx requires complex procedures, including pancreas procurement and preservation; pancreas digestion; Islet purification; and Transplantation. Even with the dramatic progresses in each of the procedures listed above, there are still challenges to make ICTx the standard therapy. These challenges are: (1) obtaining enough Islets from a single donor and (2) preventing graft loss due to allogenic rejection and recurrence of autoimmune Islet destruction. A new preservation strategy for pancreata and pancreatic ducts using ET-Kyoto solution as well as a new Islet purification method using iodixanol has substantially improved Islet yields. Continuous research to improve the efficacy of Islet isolation will solve the issue of obtaining enough Islets from a single donor. Immunological tolerance is an ideal solution for the issue of rejection and autoimmune recurrence and a regulatory T Cell strategy seems promising. Moreover, the SUITO index is a simple and powerful tool to assess engrafted Islet mass and is, therefore, useful for evaluating the efficacy of new immunosuppressant strategies. Once ICTx becomes a standard treatment, the donor shortage will become the next challenge. Marginal or living donor Islet Transplantations could help alleviate this issue; however, bio-artificial Islet Transplantation with animal Islets could be the ultimate solution.
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Pancreatic Islet Cell Transplantation: update and new developments.
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2007Co-Authors: Nicholas Onaca, Shinichi Matsumoto, Goran B. Klintmalm, Bashoo Naziruddin, Hirofumi Noguchi, Marlon F. LevyAbstract:Pancreatic Islet Cell Transplantation is a treatment alternative for patients with type 1 diabetes who experience hypoglycemic unawareness despite maximal care. The good results obtained by the group from Edmonton and other centers, with 80% insulin independence at 1 year posttransplant, are not sustainable over time, with 5-year insulin independence achieved in only 10% of patients. However, persistent graft function, even without insulin independence, results in improved glucose control and avoidance of hypoglycemic events. Changes in organ preservation, Islet processing technique, and immunosuppression regimens can result in improvement of results in the future. Islet autoTransplantation is an option for patients who undergo total pancreatectomy for chronic pancreatitis with debilitating pain, in which reinfusion of the Islets from the resected pancreas can result in avoidance of postsurgical diabetes or enhanced glucose control.
