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- Dekki, N, et al.
(author)
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Type 1 diabetic serum interferes with pancreatic beta-cell Ca2+-handling
- 2007
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In: Bioscience reports. - : Portland Press Ltd.. - 0144-8463 .- 1573-4935. ; 27:6, s. 321-326
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Journal article (peer-reviewed)abstract
- The aim of this study was to clarify the frequency of patients with type 1 diabetes that have serum that increases pancreatic β-cell cytoplasmic free Ca2+ concentration, [Ca2+]i, and if such an effect is also present in serum from first-degree relatives. We also studied a possible link between the serum effect and ethnic background as well as presence of autoantibodies. Sera obtained from three different countries were investigated as follows: 82 Swedish Caucasians with newly diagnosed type 1 diabetes, 56 Americans with different duration of type 1 diabetes, 117 American first-degree relatives of type 1 diabetic patients with a mixed ethnic background and 31 Caucasian Finnish children with newly diagnosed type 1 diabetes. Changes in [Ca2+]i, upon depolarization, were measured in β-cells incubated overnight with sera from type 1 diabetic patients, first-degree relatives or healthy controls. Our data show that there is a group constituting approximately 30% of type 1 diabetic patients of different gender, age, ethnic background and duration of the disease, as well as first-degree relatives of type 1 diabetic patients, that have sera that interfere with pancreatic β-cell Ca2+-handling. This effect on β-cell [Ca2+]i could not be correlated to the presence of autoantibodies. In a defined subgroup of patients with type 1 diabetes and first-degree relatives a defect Ca2+-handling may aggravate development of β-cell destruction.
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- Estrada, EJ, et al.
(author)
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Combined treatment of intrapancreatic autologous bone marrow stem cells and hyperbaric oxygen in type 2 diabetes mellitus
- 2008
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In: Cell transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 17:12, s. 1295-1304
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Journal article (peer-reviewed)abstract
- The objective of this study was to determine whether the combination therapy of intrapancreatic autologous stem cell infusion (ASC) and hyperbaric oxygen treatment (HBO) before and after ASC can improve islet function and metabolic control in patients with type 2 diabetes mellitus (T2DM). This prospective phase 1 study enrolled 25 patients with T2DM who received a combination therapy of intrapancreatic ASC and periinfusion HBO between March 2004 and October 2006 at Stem Cells Argentina Medical Center Buenos Aires, Argentina. Clinical variables (body mass index, oral hypoglycemic drugs, insulin requirement) and metabolic variables (fasting plasma glucose, C-peptide, HbA1c, and calculation of C-peptide/glucose ratio) were assessed over quartile periods starting at baseline and up to 1 year follow-up after intervention. Means were calculated in each quartile period and compared to baseline. Seventeen male and eight female patients were enrolled. Baseline variables expressed as means ± SEs were: age 55 ± 2.14 years, diabetes duration 13.2 ± 1.62 years, insulin dose 34.8 ± 2.96 U/day, and BMI 27.11 ± 0.51. All metabolic variables showed significant improvement when comparing baseline to 12 months follow-up, respectively: fasting glucose 205.6 ± 5.9 versus 105.2 ± 14.2 mg/dl, HbA1c 8.8 ± 0.2 versus 6.0 ± 0.4%, fasting C-peptide 1.5 ± 0.2 versus 3.3 ± 0.3 ng/ml, C-peptide/glucose ratio 0.7 ± 0.2 versus 3.5 ± 0.3, and insulin requirements 34.8 ± 2.9 versus 2.5 ± 6.7 U/day. BMI remained constant over the 1-year follow-up. Combined therapy of intrapancreatic ASC infusion and HBO can improve metabolic control and reduce insulin requirements in patients with T2DM. Further randomized controlled clinical trials will be required to confirm these findings.
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- Markmann, James F., et al.
(author)
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Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of beta-Cell Replacement
- 2016
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 100:7, s. E25-E31
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Research review (peer-reviewed)abstract
- The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.
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- Cabrera, O, et al.
(author)
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Automated, High-Throughput Assays for Evaluation of Human Pancreatic Islet Function
- 2007
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In: Cell transplantation. - : SAGE Publications. - 1555-3892 .- 0963-6897. ; 16:10, s. 1039-1048
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Journal article (peer-reviewed)abstract
- An important challenge in pancreatic islet transplantation in association with type 1 diabetes is to define automatic high-throughput assays for evaluation of human islet function. The physiological techniques presently used are amenable to small-scale experimental samples and produce descriptive results. The postgenomic era provides an opportunity to analyze biological processes on a larger scale, but the transition to high-throughput technologies is still a challenge. As a first step to implement high-throughput assays for the study of human islet function, we have developed two methodologies: multiple automated perifusion to determine islet hormone secretion and high-throughput kinetic imaging to examine islet cellular responses. Both technologies use fully automated devices that allow performing simultaneous experiments on multiple islet preparations. Our results illustrate that these technologies can be applied to study the functional status and explore the pharmacological profiles of islet cells. These methodologies will enable functional characterization of human islet preparations before transplantation and thereby provide the basis for the establishment of predictive tests for β-cell potency.
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- Fort, A, et al.
(author)
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Biohybrid devices and encapsulation technologies for engineering a bioartificial pancreas
- 2008
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In: Cell transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 17:9, s. 997-1003
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Journal article (peer-reviewed)abstract
- The use of cell-based treatments in the field of metabolic organs, particularly the pancreas, has seen tremendous growth in recent years. The transplantation of islet of Langerhans cells for the treatment of type 1 diabetes mellitus (T1DM) has allowed for natural glycemic control for patients plagued with hypoglycemia unawareness. The transplantation of islet cells into the portal vein of the liver, however, has presented challenges to the survival of the cells due to inflammation, vascularization, the need for systemic immunosuppression, and physical stress on the graft. New advances in the engineering of appropriate biohybrid devices and encapsulation technologies have led to promising alternatives to traditional methods.
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- Nolan, K, et al.
(author)
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Tissue engineering and biomaterials in regenerative medicine
- 2008
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In: Cell transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 17:3, s. 241-243
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Journal article (peer-reviewed)abstract
- The field of regenerative medicine offers the potential to significantly impact a wide spectrum of healthcare issues, from diabetes to cardiovascular disease. In particular, the design of tailored biomaterials, which possess properties desired for their particular application, and the development of superior implant environments, which seek to meet the nutritional needs of the tissue, have yielded promising tissue engineering prototypes. In this commentary, we examine the novel approaches researchers have made in customized biomaterials and promoting angiogenesis that have led to significant advancements in recent years.
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- Rodriguez-Diaz, R, et al.
(author)
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Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function
- 2012
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:52, s. 21456-21461
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Journal article (peer-reviewed)abstract
- The autonomic nervous system is thought to modulate blood glucose homeostasis by regulating endocrine cell activity in the pancreatic islets of Langerhans. The role of islet innervation, however, has remained elusive because the direct effects of autonomic nervous input on islet cell physiology cannot be studied in the pancreas. Here, we used an in vivo model to study the role of islet nervous input in glucose homeostasis. We transplanted islets into the anterior chamber of the eye and found that islet grafts became densely innervated by the rich parasympathetic and sympathetic nervous supply of the iris. Parasympathetic innervation was imaged intravitally by using transgenic mice expressing GFP in cholinergic axons. To manipulate selectively the islet nervous input, we increased the ambient illumination to increase the parasympathetic input to the islet grafts via the pupillary light reflex. This reduced fasting glycemia and improved glucose tolerance. These effects could be blocked by topical application of the muscarinic antagonist atropine to the eye, indicating that local cholinergic innervation had a direct effect on islet function in vivo. By using this approach, we found that parasympathetic innervation influences islet function in C57BL/6 mice but not in 129X1 mice, which reflected differences in innervation densities and may explain major strain differences in glucose homeostasis. This study directly demonstrates that autonomic axons innervating the islet modulate glucose homeostasis.
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