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Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes

CELL STEM CELL (2023)

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Article Endocrinology & Metabolism

Factors associated with favourable 5 year outcomes in islet transplant alone recipients with type 1 diabetes complicated by severe hypoglycaemia in the Collaborative Islet Transplant Registry

Bernhard J. Hering et al.

Summary: The study identified four factors associated with the highest rates of favorable outcomes in islet transplantation for recipients with type 1 diabetes complicated by severe hypoglycemic events. Meeting these criteria resulted in significantly improved glycemic control and a reduced risk of adverse events, showing the potential benefits of islet transplantation in this specific subgroup of type 1 diabetes patients.

DIABETOLOGIA (2023)

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Article Endocrinology & Metabolism

Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets

Zhen Liang et al.

Summary: This study demonstrates the successful implantation of human pluripotent stem cell-derived islets in a new transplantation site in the abdomen, leading to improved glycemic control in diabetic primates. The results suggest the potential of using this transplantation site for human pluripotent stem cell-based therapies for diabetes.

NATURE METABOLISM (2023)

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Article Biochemistry & Molecular Biology

Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates

Yuanyuan Du et al.

Summary: In this study, human chemically induced pluripotent stem cell-derived islets (hCiPSC-islets) were used to treat diabetes in non-human primates. The results showed that a one-dose infusion of hCiPSC-islets effectively restored insulin secretion and improved glycemic control. This study demonstrates the feasibility of hCiPSC-islets for diabetic treatment in a preclinical context.

NATURE MEDICINE (2022)

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Article Multidisciplinary Sciences

Cryopreservation and post-thaw characterization of dissociated human islet cells

Leah A. Marquez-Curtis et al.

Summary: The objective of this study was to optimize the cryopreservation of dissociated islet cells and obtain functional cells for single-cell transcriptome studies on diabetes. The optimized procedure maintained the integrity, molecular, and functional phenotypes of the cells. These findings are important for investigating cellular mechanisms in diabetes and for bio-engineering applications.

PLOS ONE (2022)

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Article Multidisciplinary Sciences

Human expandable pancreatic progenitor-derived β cells ameliorate diabetes

Xiaojie Ma et al.

Summary: Through chemical screening, the BET inhibitor I-BET151 is found to promote the expansion of pancreatic progenitors (PPs) and facilitate their differentiation into functional beta cells. Transplantation of these cells shows promising results in ameliorating diabetes. The study highlights the significance of epigenetic and transcriptional modulations in lineage-specific progenitor self-renewal.

SCIENCE ADVANCES (2022)

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Review Cell & Tissue Engineering

Biomaterials to enhance stem cell transplantation

Bhushan N. Kharbikar et al.

Summary: The successful transplantation of stem cells has the potential to revolutionize regenerative medicine, but it faces challenges such as poor cell survival and integration. Fortunately, advances in biomaterials can enhance the outcomes of stem cell transplantation.

CELL STEM CELL (2022)

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Article Biotechnology & Applied Microbiology

Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells

Diego Balboa et al.

Summary: Transplanting pancreatic islet cells derived from human pluripotent stem cells has great potential for treating diabetes. This study generated functionally mature stem-cell-derived islets (SC-islets) using an optimized protocol and compared them comprehensively to primary adult islets. The results showed that SC-islets exhibited similar functional properties to adult islets in terms of insulin secretion, electrophysiology, signaling, and exocytosis. Additionally, single-cell transcriptomics revealed a continuous maturation trajectory of SC-islets in vitro and during engraftment in mice, closely resembling that of primary islets.

NATURE BIOTECHNOLOGY (2022)

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Article Biochemistry & Molecular Biology

Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation

Li Zhan et al.

Summary: By optimizing cryoprotectant agent composition and vitrification and rewarming methods, researchers have achieved high-quality cryopreservation of islets in mouse, porcine, human, and human stem cell-derived beta cell islets. The cryopreserved islets showed high viability and normal function, suggesting that cryopreservation could be used to supply needed islets for successful transplantation and diabetes cure.

NATURE MEDICINE (2022)

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Article Cell & Tissue Engineering

Differential Function and Maturation of Human Stem Cell-Derived Islets After Transplantation

Kristina G. Maxwell et al.

Summary: The transplantation of 2 and 5 million SC-islet cells successfully reversed diabetes in mice with pre-existing diabetes, while 0.75 million cells did not. Subcutaneous and intramuscular injections failed to reverse diabetes and had undetectable expression of maturation markers. SC-islets showed similar function and maturation regardless of diabetic state.

STEM CELLS TRANSLATIONAL MEDICINE (2022)

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Article Endocrinology & Metabolism

Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada

Braulio A. Marfil-Garza et al.

Summary: This study reports the long-term outcomes of islet transplantation in a single-center cohort, including patient survival, graft survival, insulin independence, glycemic control, and adverse events. The study found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes.

LANCET DIABETES & ENDOCRINOLOGY (2022)

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Article Cell & Tissue Engineering

GP2-enriched pancreatic progenitors give rise to functional beta cells in vivo and eliminate the risk of teratoma formation

Yasaman Aghazadeh et al.

Summary: Pancreatic progenitor cells derived from human pluripotent stem cells can be purified using glycoprotein 2 enrichment, leading to the generation of functional beta cells and reducing the risk of teratomas.

STEM CELL REPORTS (2022)

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Article Cell & Tissue Engineering

Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates 13 cell differentiation

Akiko Nakamura et al.

Summary: In this study, a protocol for long-term expansion of human pancreatic progenitors in a defined medium was developed, and a polymer that can replace fibronectin was identified. The expanded progenitors showed more efficient differentiation into glucose-responsive 13 cells and produced fewer glucagon-expressing cells compared to directly differentiated progenitors. This method provides flexibility in research and therapeutic production by allowing the expansion and cryopreservation of progenitors under defined conditions.

STEM CELL REPORTS (2022)

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Article Cell & Tissue Engineering

Genetic manipulation of stress pathways can protect stem-cell-derived islets from apoptosis in vitro

Nayara C. Leite et al.

Summary: The production of SC-islets has potential for treating diabetes, but alloimmune and autoimmune responses are still challenges. Beta-cell stress may lead to immunogenicity and death, and manipulating certain genes can enhance the protection of SC-islets.

STEM CELL REPORTS (2022)

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Article Multidisciplinary Sciences

FasL microgels induce immune acceptance of islet allografts in nonhuman primates

Ji Lei et al.

Summary: We report a strategy of cotransplanting allogeneic islets and streptavidin (SA)-FasL-presenting microgels to the omentum under transient rapamycin monotherapy, which resulted in robust glycemic control, sustained C-peptide levels, and graft survival in diabetic nonhuman primates. This localized immunomodulatory strategy shows translational potential in beta cell replacement for treating type 1 diabetes.

SCIENCE ADVANCES (2022)

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Article Genetics & Heredity

Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells

Foad J. Rouhani et al.

Summary: The study explores human induced pluripotent stem cells derived from different tissues, finding UV-related damage and mutations in skin fibroblast-derived cells, while blood-derived cells show a high prevalence of acquired mutations.

NATURE GENETICS (2022)

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Review Cell Biology

Characterization of stem-cell-derived islets during differentiation and after implantation

Nerea Cuesta-Gomez et al.

Summary: Recapitulation of embryonic pancreatic development has led to the development of methods for in vitro differentiation of islet cells using human pluripotent stem cells, offering a potential cure for diabetes. Recent advancements in generating stem cell-derived islets have shown success in reversing diabetes in rodents and have shown promising results in early clinical trials. The safety concerns associated with off-target growth due to contaminated residual cells have been discussed and methods for enriching endocrine populations and removing off-target cells have been explored. The importance of quality control and release criteria testing before transplantation to ensure product safety has also been discussed.

CELL REPORTS (2022)

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Article Cell & Tissue Engineering

Whole-genome CRISPR screening identifies genetic manipulations to reduce immune rejection of stem cell-derived islets

Elad Sintov et al.

Summary: Human embryonic stem cells (hESCs) provide opportunities for cell replacement therapy, but preventing immune rejection remains a challenge. By studying the immune interaction of stem cell-derived islets (SC-islets) with peripheral blood mononuclear cells (PBMCs), researchers identified the interferon pathway as a major contributor to immune rejection. Targeting IFN-induced mediators improved SC-islet survival, and depleting CXCL10 enhanced survival against allo-rejection.

STEM CELL REPORTS (2022)

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Review Endocrinology & Metabolism

Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis

Abhishek Kulkarni et al.

Summary: The pathogenesis of diabetes varies between type 1 and type 2, but dysfunction and death of insulin-producing beta-cells are common to all forms of diabetes. Recent studies have advanced our understanding of the molecular pathways that contribute to beta-cell demise, including endoplasmic reticulum stress, integrated stress response, oxidative stress, and impaired autophagy. Animal models have been instrumental in identifying genes and proteins involved in beta-cell dysfunction during diabetes.

ENDOCRINOLOGY (2022)

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Article Biology

Exosome loaded immunomodulatory biomaterials alleviate local immune response in immunocompetent diabetic mice post islet xenotransplantation

M. Rezaa Mohammadi et al.

Summary: In a study, hybrid alginate microcapsules (AlgXOs) releasing exosomes derived from human umbilical cord mesenchymal stem cells (XOs) were shown to attenuate immune response post-implantation. The XOs suppressed local immune microenvironment and immune cell activity, leading to significant efficacy in a mouse model of Type 1 Diabetes. The results suggest that the controlled release of XOs from AlgXOs could alleviate the local immune response to implantable biomaterials.

COMMUNICATIONS BIOLOGY (2021)

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Review Endocrinology & Metabolism

The promise of stem cell-derived islet replacement therapy

Douglas Melton

Summary: Current treatments for diabetes involve multiple insulin injections and islet transplantation, however, the use of pluripotent stem cells to produce human islet-like clusters may offer a potential alternative method for treatment.

DIABETOLOGIA (2021)

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Article Cell & Tissue Engineering

Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes

Adam Ramzy et al.

Summary: This study evaluates the safety and efficacy of implanting pancreatic endoderm cells for treating type 1 diabetes, showing increased C-peptide levels and mature beta cell phenotype in grafts after implantation. The findings provide evidence of meal-regulated insulin secretion by differentiated stem cells in patients.

CELL STEM CELL (2021)

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Review Medicine, Research & Experimental

Insulin signaling in health and disease

Alan R. Saltiel

Summary: The molecular mechanisms of cellular insulin action involve binding of insulin to its receptor, activation of tyrosine kinase activity, phosphorylation of intracellular substrates to initiate signaling pathways, and control of various cellular processes to maintain glucose homeostasis.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Multidisciplinary Sciences

Organoid microphysiological system preserves pancreatic islet function within 3D matrix

S. N. Patel et al.

Summary: This study highlights the importance of a dynamic in vitro microenvironment for preserving the function of primary organoid models and demonstrates the utility of the MPS for in situ multiparametric assessment.

SCIENCE ADVANCES (2021)

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Review Medicine, Research & Experimental

Type 1 diabetes mellitus: much progress, many opportunities

Alvin C. Powers

Summary: Type 1 diabetes is a result of autoimmune response requiring lifelong insulin therapy. Although there is considerable heterogeneity in genetics, pathology, and clinical course of T1D, there are still knowledge gaps and opportunities for improving understanding of its pathogenesis. Emerging therapies are being developed to treat or prevent T1D.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Multidisciplinary Sciences

An inverse-breathing encapsulation system for cell delivery

Long-Hai Wang et al.

Summary: The study introduces an encapsulation system that produces oxygen for cells from carbon dioxide in a self-regulated manner, improving cell survival in hypoxic conditions. Through simulation-guided optimization, the device successfully maintained normoglycemia in animal experiments, demonstrating its potential to support long-term cellular function.

SCIENCE ADVANCES (2021)

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Review Engineering, Biomedical

Designing biomaterials for the modulation of allogeneic and autoimmune responses to cellular implants in Type 1 Diabetes

Magdalena M. Samojlik et al.

Summary: Effective suppression of adaptive immune responses is crucial for the success of allogeneic cell therapies, especially in the presence of pre-existing autoimmunity. Current immunosuppressive agents used in islet transplantation show limitations in controlling memory T cell populations, leaving the graft vulnerable. Biomaterials have the potential to provide local and nuanced instruction to suppress immune pathways and improve the efficacy of cell therapy.

ACTA BIOMATERIALIA (2021)

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Article Cell & Tissue Engineering

Mouse Pluripotent Stem Cell Differentiation Under Physiological Oxygen Reduces Residual Teratomas

Jeffrey R. Millman et al.

Summary: Control of oxygen partial pressure (pO(2)) to physiological levels on a highly oxygen permeable substrate can reduce the fraction of pluripotent stem cells (PSC) within differentiated populations and their tumorigenic potential. This method, alone or in combination with cell sorting, shows promise for minimizing tumor formation in future cell therapy protocols.

CELLULAR AND MOLECULAR BIOENGINEERING (2021)

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Review Transplantation

Update on islet cell transplantation

Kevin Verhoeff et al.

Summary: Chronic diabetes-related complications continue to strain global healthcare systems, with islet cell transplantation offering a promising approach to reduce hypoglycemic risks and provide optimal glycemic control, but facing limitations in tissue sources and the need for chronic immunosuppression. Advances in stem cell-based therapies show potential for overcoming these challenges, but regional access variability and ethical questions regarding commercialization need to be addressed for widespread use.

CURRENT OPINION IN ORGAN TRANSPLANTATION (2021)

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Article Biochemical Research Methods

Generation of insulin-producing pancreatic β cells from multiple human stem cell lines

Nathaniel J. Hogrebe et al.

Summary: The study presents a six-stage differentiation methodology for generating insulin-secreting pancreatic beta cells from human pluripotent stem cells. This protocol allows for the efficient production of functional SC-beta cells in vitro, opening up new possibilities for future research and therapeutic applications.

NATURE PROTOCOLS (2021)

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Review Biotechnology & Applied Microbiology

Engineering islets from stem cells for advanced therapies of diabetes

Johanna Siehler et al.

Summary: Diabetes is a significant global health concern affecting millions of people, and advanced therapies utilizing stem cell differentiation and islet engineering may offer potential breakthroughs in treatment. Research in these areas could lead to improved understanding of pancreatic function and provide new insights into diabetes mechanisms.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Article Multidisciplinary Sciences

A therapeutic convection-enhanced macroencapsulation device for enhancing β cell viability and insulin secretion

Kisuk Yang et al.

Summary: Traditional islet transplantation for type 1 diabetes treatment has been hindered by lifelong immunosuppression, however, new convective nutrient transport technology shows potential to increase loading capacity, promote cell viability, and improve insulin secretion and fibrosis reduction for diabetic patients.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Cell Biology

A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes

Xi Wang et al.

Summary: The study introduces a novel device composed of nanofibers for transplanting stem cell-derived beta cells to treat T1D, demonstrating its safety, efficacy, and sustainability in animal experiments.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Cell Biology

Selective deletion of human leukocyte antigens protects stem cell-derived islets from immune rejection

Audrey Parent et al.

Summary: The use of genetic engineering to create hypoimmunogenic human pluripotent stem cells (hPSCs) has shown promise in reducing alloimmune rejection and allowing for better matching with recipients in the treatment of type 1 diabetes.

CELL REPORTS (2021)

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Review Chemistry, Multidisciplinary

Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes

Debkalpa Goswami et al.

Summary: Stem cell derived insulin producing cells or islets show promise in reversing Type 1 Diabetes (T1D), but successful transplantation currently requires long-term modulation with immunosuppressant drugs. An alternative approach to avoid immune response is to use an islet macroencapsulation device. These systems must meet stringent design criteria to achieve the ultimate goal of reversing T1D.

ADVANCED SCIENCE (2021)

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Article Medicine, Research & Experimental

Improvement of islet transplantation by the fusion of islet cells with functional blood vessels

Lisa Nalbach et al.

Summary: Prevascularized islet organoids with functional microvessels can improve the success rates of clinical islet transplantation, as they exhibit higher angiogenic activity and can be rapidly blood-perfused after transplantation.

EMBO MOLECULAR MEDICINE (2021)

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Article Surgery

Pancreatic islets engineered with a FasL protein induce systemic tolerance at the induction phase that evolves into long-term graft-localized immune privilege

Kyle B. Woodward et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2020)

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Article Engineering, Biomedical

Developing mechanically robust, triazole-zwitterionic hydrogels to mitigate foreign body response (FBR) for islet encapsulation

Qingsheng Liu et al.

BIOMATERIALS (2020)

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Article Cell & Tissue Engineering

Circadian Entrainment Triggers Maturation of Human In Vitro Islets

Juan R. Alvarez-Dominguez et al.

CELL STEM CELL (2020)

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Article Biotechnology & Applied Microbiology

Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells

Nathaniel J. Hogrebe et al.

NATURE BIOTECHNOLOGY (2020)

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Article Cell Biology

Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization

Shareen Forbes et al.

SCIENCE TRANSLATIONAL MEDICINE (2020)

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Article Cell & Tissue Engineering

Pro-inflammatory cytokines induce cell death, inflammatory responses, and endoplasmic reticulum stress in human iPSC-derived beta cells

Stephane Demine et al.

STEM CELL RESEARCH & THERAPY (2020)

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Article Cell Biology

Gene-edited human stem cell-derived β cells from a patient with monogenic diabetes reverse preexisting diabetes in mice

Kristina G. Maxwell et al.

SCIENCE TRANSLATIONAL MEDICINE (2020)

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Article Cell Biology

Glucose Response by Stem Cell-Derived β Cells In Vitro Is Inhibited by a Bottleneck in Glycolysis

Jeffrey C. Davis et al.

CELL REPORTS (2020)

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Article Biotechnology & Applied Microbiology

Generation of pancreatic β cells from CD177+ anterior definitive endoderm

Pallavi U. Mahaddalkar et al.

NATURE BIOTECHNOLOGY (2020)

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Review Endocrinology & Metabolism

Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure

Decio L. Eizirik et al.

NATURE REVIEWS ENDOCRINOLOGY (2020)

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Editorial Material Cell & Tissue Engineering

Solving the Puzzle of Immune Tolerance for beta-Cell Replacement Therapy for Type 1 Diabetes

Jeffrey A. Bluestone et al.

CELL STEM CELL (2020)

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Article Multidisciplinary Sciences

Immune-evasive human islet-like organoids ameliorate diabetes

Eiji Yoshihara et al.

NATURE (2020)

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Article Cell Biology

Single-Cell Transcriptome Profiling Reveals β Cell Maturation in Stem Cell-Derived Islets after Transplantation

Punn Augsornworawat et al.

CELL REPORTS (2020)

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Article Multidisciplinary Sciences

Immunotherapy via PD-L1-presenting biomaterials leads to long-term islet graft survival

Maria M. Coronel et al.

SCIENCE ADVANCES (2020)

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Article Endocrinology & Metabolism

Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation

Chen Weng et al.

NATURE METABOLISM (2020)

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Article Materials Science, Biomaterials

Bioengineering a pre-vascularized pouch for subsequent islet transplantation using VEGF-loaded polylactide capsules

Naresh Kasoju et al.

BIOMATERIALS SCIENCE (2020)

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Review Cell Biology

Navigating Two Roads to Glucose Normalization in Diabetes: Automated Insulin Delivery Devices and Cell Therapy

Esther Latres et al.

CELL METABOLISM (2019)

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Article Multidisciplinary Sciences

The single-cell transcriptional landscape of mammalian organogenesis

Junyue Cao et al.

NATURE (2019)

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Article Biotechnology & Applied Microbiology

Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients

Tobias Deuse et al.

NATURE BIOTECHNOLOGY (2019)

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Article Cell Biology

Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells

Gopika G. Nair et al.

NATURE CELL BIOLOGY (2019)

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Article Multidisciplinary Sciences

Chemically defined conditions for long-term maintenance of pancreatic progenitors derived from human induced pluripotent stem cells

Shuhei Konagaya et al.

SCIENTIFIC REPORTS (2019)

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Article Multidisciplinary Sciences

Charting cellular identity during human in vitro β-cell differentiation

Adrian Veres et al.

NATURE (2019)

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Article Multidisciplinary Sciences

Generation of hypoimmunogenic human pluripotent stem cells

Xiao Han et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Cell Biology

Wnt Signaling Separates the Progenitor and Endocrine Compartments during Pancreas Development

Nadav Sharon et al.

CELL REPORTS (2019)

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Article Engineering, Biomedical

Oxygen generating biomaterial improves the function and efficacy of beta cells within a macroencapsulation device

M. M. Coronel et al.

BIOMATERIALS (2019)

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Article Chemistry, Physical

Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations

Shady Farah et al.

NATURE MATERIALS (2019)

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Review Genetics & Heredity

BCOR involvement in cancer

Annalisa Astolfi et al.

EPIGENOMICS (2019)

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Article Multidisciplinary Sciences

YAP inhibition enhances the differentiation of functional stem cell-derived insulin-producing β cells

Edwin A. Rosado-Olivieri et al.

NATURE COMMUNICATIONS (2019)

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Article Endocrinology & Metabolism

Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study

Marie-Christine Vantyghem et al.

DIABETES CARE (2019)

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Article Multidisciplinary Sciences

Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes

Fanny Lebreton et al.

NATURE COMMUNICATIONS (2019)

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Article Multidisciplinary Sciences

Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation

Qingsheng Liu et al.

NATURE COMMUNICATIONS (2019)

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Review Endocrinology & Metabolism

Pancreatic Islet Transplantation in Humans: Recent Progress and Future Directions

Michael R. Rickels et al.

ENDOCRINE REVIEWS (2019)

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Article Cell & Tissue Engineering

Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells

Leonardo Velazco-Cruz et al.

STEM CELL REPORTS (2019)

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Article Surgery

Alginate-microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression

David A. Alagpulinsa et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2019)

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Review Cell Biology

Biochemical and cellular properties of insulin receptor signalling

Rebecca A. Haeusler et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2018)

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Article Surgery

Transplantation of macroencapsulated human islets within the bioartificial pancreas Air to patients with type 1 diabetes mellitus

Per-Ola Carlsson et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2018)

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Review Cell Biology

The cell biology of systemic insulin function

Victoria L. Tokarz et al.

JOURNAL OF CELL BIOLOGY (2018)

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Article Chemistry, Physical

Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance

Devon M. Headen et al.

NATURE MATERIALS (2018)

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Article Endocrinology & Metabolism

Stem cells and beta cell replacement therapy: a prospective health technology assessment study

Klemens Wallner et al.

BMC ENDOCRINE DISORDERS (2018)

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Review Endocrinology & Metabolism

The journey of islet cell transplantation and future development

Anissa Gamble et al.

ISLETS (2018)

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Article Endocrinology & Metabolism

Systematic review of islet cryopreservation

Greg G. Kojayan et al.

ISLETS (2018)

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Article Engineering, Biomedical

Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques

Matthew A. Bochenek et al.

NATURE BIOMEDICAL ENGINEERING (2018)

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Article Multidisciplinary Sciences

Linking a cell-division gene and a suicide gene to define and improve cell therapy safety

Qin Liang et al.

NATURE (2018)

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Article Multidisciplinary Sciences

Mechanosignalling via integrins directs fate decisions of pancreatic progenitors

Anant Mamidi et al.

NATURE (2018)

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Review Biotechnology & Applied Microbiology

Advances In islet encapsulation technologies

Tejal Desai et al.

NATURE REVIEWS DRUG DISCOVERY (2017)

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Article Multidisciplinary Sciences

Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations

Florian T. Merkle et al.

NATURE (2017)

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Article Biotechnology & Applied Microbiology

HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells

German G. Gornalusse et al.

NATURE BIOTECHNOLOGY (2017)

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Letter Medicine, General & Internal

Bioengineering of an Intraabdominal Endocrine Pancreas

David A. Baidal et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Article Multidisciplinary Sciences

Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets

Alexander E. Vlahos et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

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Article Cell & Tissue Engineering

Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells

Jamie Trott et al.

STEM CELL REPORTS (2017)

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Article Cell & Tissue Engineering

Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives

Go Itakura et al.

STEM CELL REPORTS (2017)

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Article Cell & Tissue Engineering

Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

Andrew R. Pepper et al.

STEM CELL REPORTS (2017)

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Article Cell & Tissue Engineering

Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant

Gaetano Faleo et al.

STEM CELL REPORTS (2017)

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Article Multidisciplinary Sciences

Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites

Jessica D. Weaver et al.

SCIENCE ADVANCES (2017)

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Review Biochemistry & Molecular Biology

The immune response to secondary necrotic cells

Monika Sachet et al.

APOPTOSIS (2017)

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Article Biology

Long-term cryopreservation of reaggregated pancreatic islets resulting in successful transplantation in rats

Sonia Rawal et al.

CRYOBIOLOGY (2017)

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Article Surgery

Long-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States

D. C. Brennan et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2016)

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Article Surgery

A Comparative Analysis of the Safety, Efficacy, and Cost of Islet Versus Pancreas Transplantation in Nonuremic Patients With Type 1 Diabetes

S. Moassesfar et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2016)

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Article Endocrinology & Metabolism

Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold

Dora M. Berman et al.

DIABETES (2016)

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Article Medicine, Research & Experimental

Stress-impaired transcription factor expression and insulin secretion in transplanted human islets

Chunhua Dai et al.

JOURNAL OF CLINICAL INVESTIGATION (2016)

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Editorial Material Multidisciplinary Sciences

Encapsulating the problem

Elie Dolgin

NATURE (2016)

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Article Biotechnology & Applied Microbiology

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

Arturo J. Vegas et al.

NATURE BIOTECHNOLOGY (2016)

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Article Biochemistry & Molecular Biology

Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice

Arturo J. Vegas et al.

NATURE MEDICINE (2016)

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Review Endocrinology & Metabolism

Impact of islet architecture on β-cell heterogeneity, plasticity and function

Sara S. Roscioni et al.

NATURE REVIEWS ENDOCRINOLOGY (2016)

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Article Surgery

Long-Term Immunosuppression After Solitary Islet Transplantation Is Associated With Preserved C-Peptide Secretion for More Than a Decade

J. E. Blau et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2015)

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Article Biochemistry & Molecular Biology

Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro

Holger A. Russ et al.

EMBO JOURNAL (2015)

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Article Multidisciplinary Sciences

Single-cell chromatin accessibility reveals principles of regulatory variation

Jason D. Buenostro et al.

NATURE (2015)

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Article Biotechnology & Applied Microbiology

A prevascularized subcutaneous device-less site for islet and cellular transplantation

Andrew R. Pepper et al.

NATURE BIOTECHNOLOGY (2015)

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News Item Biotechnology & Applied Microbiology

RIKEN suspends first clinical trial involving induced pluripotent stem cells

Ken Garber

NATURE BIOTECHNOLOGY (2015)

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Article Cell Biology

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors

Ines Cebola et al.

NATURE CELL BIOLOGY (2015)

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Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates

Omid Veiseh et al.

NATURE MATERIALS (2015)

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Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing

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SCIENCE (2015)

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Efficient CRISPR-Cas9-Mediated Generation of Knockin Human Pluripotent Stem Cells Lacking Undesired Mutations at the Targeted Locus

Florian T. Merkle et al.

CELL REPORTS (2015)

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Article Cell & Tissue Engineering

Insulin-Producing Endocrine Cells Differentiated In Vitro From Human Embryonic Stem Cells Function in Macroencapsulation Devices In Vivo

Alan D. Agulnick et al.

STEM CELLS TRANSLATIONAL MEDICINE (2015)

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Article Cell & Tissue Engineering

Efficient Generation of NKX6-1+ Pancreatic Progenitors from Multiple Human Pluripotent Stem Cell Lines

M. Cristina Nostro et al.

STEM CELL REPORTS (2015)

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Polymers in cell encapsulation from an enveloped cell perspective

Paul de Vos et al.

ADVANCED DRUG DELIVERY REVIEWS (2014)

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Review Pharmacology & Pharmacy

Encapsulated islets for diabetes therapy: History, current progress, and critical issues requiring solution

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Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts

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AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM (2014)

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Generation of Functional Human Pancreatic β Cells In Vitro

Felicia W. Pagliuca et al.

CELL (2014)

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Article Cell & Tissue Engineering

Low Incidence of Off-Target Mutations in Individual CRISPR-Cas9 and TALEN Targeted Human Stem Cell Clones Detected by Whole-Genome Sequencing

Adrian Veres et al.

CELL STEM CELL (2014)

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Article Endocrinology & Metabolism

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: Overview

David M. Nathan

DIABETES CARE (2014)

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Article Biotechnology & Applied Microbiology

Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells

Alireza Rezania et al.

NATURE BIOTECHNOLOGY (2014)

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Article Multidisciplinary Sciences

Flow Characterization of a Spinner Flask for Induced Pluripotent Stem Cell Culture Application

Mohd-Zulhilmi Ismadi et al.

PLOS ONE (2014)

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Article Multidisciplinary Sciences

Differentiated human stem cells resemble fetal, not adult, β cells

Sinisa Hrvatin et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

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Article Cell & Tissue Engineering

Human embryonic stem cell derived islet progenitors mature inside an encapsulation device without evidence of increased biomass or cell escape

Kaitlyn Kirk et al.

STEM CELL RESEARCH (2014)

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Article Cell & Tissue Engineering

The TheraCyte (TM) Device Protects Against Islet Allograft Rejection in Immunized Hosts

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CELL TRANSPLANTATION (2013)

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Article Cell & Tissue Engineering

Enhanced Oxygen Supply Improves Islet Viability in a New Bioartificial Pancreas

Uriel Barkai et al.

CELL TRANSPLANTATION (2013)

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Article Endocrinology & Metabolism

Improvement in β-Cell Secretory Capacity After Human Islet Transplantation According to the CIT07 Protocol

Michael R. Rickels et al.

DIABETES (2013)

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Article Endocrinology & Metabolism

Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice

Jennifer E. Bruin et al.

DIABETOLOGIA (2013)

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Review Cell Biology

p53 mutations in cancer

Patricia A. J. Muller et al.

NATURE CELL BIOLOGY (2013)

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Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position

Jason D. Buenrostro et al.

NATURE METHODS (2013)

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Review Genetics & Heredity

Single-cell sequencing-based technologies will revolutionize whole-organism science

Ehud Shapiro et al.

NATURE REVIEWS GENETICS (2013)

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Inhibition of pluripotent stem cell-derived teratoma formation by small molecules

Mi-Ok Lee et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

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Review Emergency Medicine

Diabetic Ketoacidosis: A Review and Update

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CURRENT EMERGENCY AND HOSPITAL MEDICINE REPORTS (2013)

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Article Endocrinology & Metabolism

Islet β-Cell Endoplasmic Reticulum Stress Precedes the Onset of Type 1 Diabetes in the Nonobese Diabetic Mouse Model

Sarah A. Tersey et al.

DIABETES (2012)

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Article Endocrinology & Metabolism

Maturation of Human Embryonic Stem Cell-Derived Pancreatic Progenitors Into Functional Islets Capable of Treating Pre-existing Diabetes in Mice

Alireza Rezania et al.

DIABETES (2012)

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Editorial Material Endocrinology & Metabolism

Severe Hypoglycemia Predicts Mortality in Diabetes

Philip E. Cryer

DIABETES CARE (2012)

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Article Endocrinology & Metabolism

Improvement in Outcomes of Clinical Islet Transplantation: 1999-2010

Franca B. Barton et al.

DIABETES CARE (2012)

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Article Endocrinology & Metabolism

Induction of beta-cell resistance to hypoxia and technologies for oxygen delivery to transplanted pancreatic islets

Daniel Lazard et al.

DIABETES-METABOLISM RESEARCH AND REVIEWS (2012)

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Article Multidisciplinary Sciences

Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials

Eileen Pedraza et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

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Article Medicine, Research & Experimental

Update on Islet Transplantation

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COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2012)

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Dynamic Changes in the Copy Number of Pluripotency and Cell Proliferation Genes in Human ESCs and iPSCs during Reprogramming and Time in Culture

Louise C. Laurent et al.

CELL STEM CELL (2011)

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Review Transplantation

Control of instant blood-mediated inflammatory reaction to improve islets of Langerhans engraftment

Bo Nilsson et al.

CURRENT OPINION IN ORGAN TRANSPLANTATION (2011)

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Pancreatic Islets Engineered with SA-FasL Protein Establish Robust Localized Tolerance by Inducing Regulatory T Cells in Mice

Esma S. Yolcu et al.

JOURNAL OF IMMUNOLOGY (2011)

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Article Multidisciplinary Sciences

Somatic coding mutations in human induced pluripotent stem cells

Athurva Gore et al.

NATURE (2011)

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Letter Biotechnology & Applied Microbiology

Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells

Seth M. Taapken et al.

NATURE BIOTECHNOLOGY (2011)

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Article Biotechnology & Applied Microbiology

Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells

Olivia G. Kelly et al.

NATURE BIOTECHNOLOGY (2011)

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Article Endocrinology & Metabolism

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats

Aleksey V. Matveyenko et al.

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM (2010)

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Article Endocrinology & Metabolism

Clinical and Experimental Pancreatic Islet Transplantation to Striated Muscle Establishment of a Vascular System Similar to That in Native Islets

Gustaf Christoffersson et al.

DIABETES (2010)

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Review Endocrinology & Metabolism

The hypoxia response pathway and beta-cell function

J. Cantley et al.

DIABETES OBESITY & METABOLISM (2010)

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Article Biochemistry & Molecular Biology

Teratomas From Plutipotent Stem Cells: A Clinical Hurdle

Chui-Yee Fong et al.

JOURNAL OF CELLULAR BIOCHEMISTRY (2010)

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Oxidative stress and beta-cell dysfunction

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PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY (2010)

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Review Cell & Tissue Engineering

Scalable Stirred-Suspension Bioreactor Culture of Human Pluripotent Stem Cells

Daniel E. Kehoe et al.

TISSUE ENGINEERING PART A (2010)

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Article Biotechnology & Applied Microbiology

Generation of Human Embryonic Stem Cell-Derived Mesoderm and Cardiac Cells Using Size-Specified Aggregates in an Oxygen-Controlled Bioreactor

Sylvia Niebruegge et al.

BIOTECHNOLOGY AND BIOENGINEERING (2009)

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Review Cell Biology

Mechanisms of biphasic insulin-granule exocytosis - roles of the cytoskeleton, small GTPases and SNARE proteins

Zhanxiang Wang et al.

JOURNAL OF CELL SCIENCE (2009)

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Review Surgery

Optimal implantation site for pancreatic islet transplantation

S. Merani et al.

BRITISH JOURNAL OF SURGERY (2008)

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Article Biotechnology & Applied Microbiology

Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo

Evert Kroon et al.

NATURE BIOTECHNOLOGY (2008)

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Review Immunology

Foreign body reaction to biomaterials

James M. Anderson et al.

SEMINARS IN IMMUNOLOGY (2008)

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Article Immunology

Positron emission tomography: A real-time tool to quantify early islet engraftment in a preclinical large animal model

Torsten Eich et al.

TRANSPLANTATION (2007)

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Article Surgery

High risk of sensitization after failed islet transplantation

P. M. Campbell et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2007)

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Letter Medicine, General & Internal

Visualization of early engraftment in clinical islet transplantation by positron-emission tomography

Torsten Eich et al.

NEW ENGLAND JOURNAL OF MEDICINE (2007)

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Review Cell & Tissue Engineering

Factors influencing the loss of beta-cell mass in islet transplantation

Juliet A. Emamaullee et al.

CELL TRANSPLANTATION (2007)

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Article Biotechnology & Applied Microbiology

Reactor engineering in large scale animal cell culture

Alvin W. Nienow

CYTOTECHNOLOGY (2006)

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Article Biotechnology & Applied Microbiology

Efficient differentiation of human embryonic stem cells to definitive endoderm

KA D'Amour et al.

NATURE BIOTECHNOLOGY (2005)

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Article Medicine, General & Internal

Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation

L Moberg et al.

LANCET (2002)

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Article Endocrinology & Metabolism

Successful islet transplantation - Continued insulin reserve provides long-term glycemic control

EA Ryan et al.

DIABETES (2002)

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Article Endocrinology & Metabolism

beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia

M Biarnes et al.

DIABETES (2002)

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Review Multidisciplinary Sciences

Insulin signalling and the regulation of glucose and lipid metabolism

AR Saltiel et al.

NATURE (2001)

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Article Surgery

Lessons learned from more than 1,000 pancreas transplants at a single institution

DER Sutherland et al.

ANNALS OF SURGERY (2001)

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Article Medicine, General & Internal

Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.

AMJ Shapiro et al.

NEW ENGLAND JOURNAL OF MEDICINE (2000)

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Article Gastroenterology & Hepatology

Cell loss in isolated human islets occurs by apoptosis

S Paraskevas et al.

PANCREAS (2000)

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