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islet,beta-cell,diabetes,stem cell

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https://www.readbyqxmd.com/read/29717618/glucocorticoid-signaling-enhances-expression-of-glucose-sensing-molecules-in-immature-pancreatic-beta-like-cells-derived-from-murine-embryonic-stem-cells-in-vitro
#1
Nadiah Ghazalli, Xiaoxing Wu, Stephanie Walker, Nancy Trieu, Li-Yu Hsin, Justin Choe, Chialin Chen, Jasper Hsu, Jeanne LeBon, Mark T Kozlowski, Jeffrey Rawson, David A Tirrell, M L Richard Yip, Hsun Teresa Ku
Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known...
May 2, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29716418/melatonin-improves-the-therapeutic-role-of-mesenchymal-stem-cells-in-diabetic-rats
#2
Marwa Hassen, Shadia M Kadry, Nawal Zakaria, Mai H El-Dakdoky
The present study was performed to investigate the role of bone marrow mesenchymal stem cells (MSCs) and/or melatonin (MT) for improvement of beta cell functions in STZ diabetic rats. Male albino rats (130-150g) were divided into six groups. CONTROL GROUP: received phosphate buffer saline (PBS); Melatonin group received melatonin (10 mg/kg b.wt./day for 2 months by oral gavage); Diabetic untreated group; Diabetic group treated with melatonin; Diabetic group treated with mesenchymal stem cells (A single intravenous injection of 3 × 106 cell in PBS) and Diabetic group co-treated with stem cells and melatonin...
May 1, 2018: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/29675567/human-urine-derived-stem-cells-play-a-novel-role-in-the-treatment-of-stz-induced-diabetic-mice
#3
Tianxue Zhao, Deng Luo, Yun Sun, Xin Niu, Yang Wang, Chen Wang, Weiping Jia
Human urine-derived stem cells (hUSCs) are a potential stem cell source for cell therapy. However, the effect of hUSCs on glucose metabolism regulation in type 1 diabetes was not clear. Therefore, the aim of the study was to evaluate whether hUSCs have protective effect on streptozotocin (STZ)-induced diabetes. hUSCs were extracted and cultivated with a special culture medium. Flow cytometry analysis was applied to detect cell surface markers. BALB/c male nude mice were either injected with high-dose STZ (HD-STZ) or multiple low-dose STZ (MLD-STZ)...
April 19, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29675560/patterns-of-differential-gene-expression-in-a-cellular-model-of-human-islet-development-and-relationship-to-type-2-diabetes-predisposition
#4
Marta Perez-Alcantara, Christian Honoré, Agata Wesolowska-Andersen, Anna L Gloyn, Mark I McCarthy, Mattias Hansson, Nicola L Beer, Martijn van de Bunt
AIMS/HYPOTHESIS: Most type 2 diabetes-associated genetic variants identified via genome-wide association studies (GWASs) appear to act via the pancreatic islet. Observed defects in insulin secretion could result from an impact of these variants on islet development and/or the function of mature islets. Most functional studies have focused on the latter, given limitations regarding access to human fetal islet tissue. Capitalising upon advances in in vitro differentiation, we characterised the transcriptomes of human induced pluripotent stem cell (iPSC) lines differentiated along the pancreatic endocrine lineage, and explored the contribution of altered islet development to the pathogenesis of type 2 diabetes...
April 19, 2018: Diabetologia
https://www.readbyqxmd.com/read/29451122/sprouting-angiogenesis-in-engineered-pseudo-islets
#5
Monika Hospodiuk, Madhuri Dey, Bugra Ayan, Donna Sosnoski, Kazim K Moncal, Yang Wu, Ibrahim T Ozbolat
Despite the recent achievements in cell-based therapies for curing type-1 diabetes (T1D), capillarization in beta (β)-cell clusters is still a major roadblock as it is essential for long-term viability and function of β-cells in vivo. In this research, we report sprouting angiogenesis in engineered pseudo islets (EPIs) made of mouse insulinoma βTC3 cells and rat heart microvascular endothelial cells (RHMVECs). Upon culturing in three-dimensional (3D) constructs under angiogenic conditions, EPIs sprouted extensive capillaries into the surrounding matrix...
March 16, 2018: Biofabrication
https://www.readbyqxmd.com/read/29394145/the-journey-of-islet-cell-transplantation-and-future-development
#6
Anissa Gamble, Andrew R Pepper, Antonio Bruni, A M James Shapiro
Intraportal islet transplantation has proven to be efficacious in preventing severe hypoglycemia and restoring insulin independence in selected patients with type 1 diabetes. Multiple islet infusions are often required to achieve and maintain insulin independence. Many challenges remain in clinical islet transplantation, including substantial islet cell loss early and late after islet infusion. Contributions to graft loss include the instant blood-mediated inflammatory reaction, potent host auto- and alloimmune responses, and beta cell toxicity from immunosuppressive agents...
March 4, 2018: Islets
https://www.readbyqxmd.com/read/29382312/stem-cells-and-beta-cell-replacement-therapy-a-prospective-health-technology-assessment-study
#7
Klemens Wallner, Rene G Pedroza, Isaac Awotwe, James M Piret, Peter A Senior, A M James Shapiro, Christopher McCabe
BACKGROUND: Although current beta cell replacement therapy is effective in stabilizing glycemic control in highly selected patients with refractory type 1 diabetes, many hurdles are inherent to this and other donor-based transplantation methods. One solution could be moving to stem cell-derived transplant tissue. This study investigates a novel stem cell-derived graft and implant technology and explores the circumstances of its cost-effectiveness compared to intensive insulin therapy...
January 30, 2018: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/29319179/muscle-derived-satellite-cells-for-treating-type-1-diabetes-in-rats-rattus-norvegicus
#8
Yu Ren, Hefei Wang, Si Ha, Xingsheng Zhao, Xiao Wang, Yu Lan, Xiaoling Liu
Diabetes mellitus(DM) is a complicated metabolic disease, with the fundamental treatment nowadays being diet control, insulin injections, slet or pancreas transplantation, which is limited because exogenous insulin injections fail to simulate normal insulin secretion in islet beta cells successfully and islet transplantation lacks organ donors. So far, stem cells with highly self-renewal and multi-directional differentiation potential have become a new hope for the treatment of diabetes. In this research, rat Muscle-derived satellite cells *MDSCs*were separated and cultivated in vitro and inducted into insulin-producing cells with observation and identification using dithizone staining and so on...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29288549/transplantation-of-macroencapsulated-human-islets-within-the-bioartificial-pancreas-%C3%AE-air-to-patients-with-type-1-diabetes-mellitus
#9
Per-Ola Carlsson, Daniel Espes, Amir Sedigh, Avi Rotem, Baruch Zimerman, Helena Grinberg, Tali Goldman, Uriel Barkai, Yuval Avni, Gunilla T Westermark, Lina Carlbom, Håkan Ahlström, Olof Eriksson, Johan Olerud, Olle Korsgren
Macroencapsulation devices provide the dual possibility of immunoprotecting transplanted cells while also being retrievable, the latter bearing importance for safety in future trials with stem cell-derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets into patients with type 1 diabetes...
December 29, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29275427/hope-vs-hype-where-are-we-in-type-1-diabetes
#10
REVIEW
Jay S Skyler
Much progress has been made in type 1 diabetes research. Biological replacement of islet function has been achieved with pancreas transplantation and with islet transplantation. In the future, human embryonic stem cells and/or induced pluripotent stem cells may offer a potentially unlimited source of cells for islet replacement. Another potential strategy is to induce robust beta cell replication so that regeneration of islets can be achieved. Immune interventions are being studied with the hope of arresting the type 1 diabetes disease process to either prevent the disease or help preserve beta cell function...
March 2018: Diabetologia
https://www.readbyqxmd.com/read/29241367/differentiation-of-conjunctiva-mesenchymal-stem-cells-into-secreting-islet-beta-cells-on-plasma-treated-electrospun-nanofibrous-scaffold
#11
Samad Nadri, Ghasem Barati, Hossein Mostafavi, Abdolreza Esmaeilzadeh, Seyed Ehsan Enderami
Transplantation of stem cells using biocompatible nanofibrous scaffolds is a promising therapeutic method for treating Diabetic Mellitus. The aim of this study was to derive insulin-producing cells (IPCs) from conjunctiva-derived mesenchymal stem cell (CJMSCs) and to compare the functionality of differentiated IPCs in a three-dimensional (3D) culture with 2D. Furthermore, the effects of hydrophobicity of scaffold on IPCs differentiation were examined. Scanning electron microscopy (SEM), quantitative real times PCR (qPCR), Immunostaining and flow cytometry were used to analyze fabricated scaffold and the presence of IPCs...
December 14, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29181780/3d-models-of-insulin-producing-%C3%AE-cells-from-primary-islet-cells-to-stem-cell-derived-islets
#12
REVIEW
Diana Ribeiro, Alexander J Kvist, Pernilla Wittung-Stafshede, Ryan Hicks, Anna Forslöw
There is a need for physiologically relevant assay platforms to provide functionally relevant models of diabetes, to accelerate the discovery of new treatment options and boost developments in drug discovery. In this review, we compare several 3D-strategies that have been used to increase the functional relevance of ex vivo human primary pancreatic islets and developments into the generation of stem cell derived pancreatic beta-cells (β-cells). Special attention will be given to recent approaches combining the use of extracellular matrix (ECM) scaffolds with pancreatic molecular memory, which can be used to improve yield and functionality of in vitro stem cell-derived pancreatic models...
November 27, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29150935/generation-of-insulin-producing-cells-from-human-adipose-derived-mesenchymal-stem-cells-on-pva-scaffold-by-optimized-differentiation-protocol
#13
Seyed Ehsan Enderami, Masoud Soleimani, Yousef Mortazavi, Samad Nadri, Ali Salimi
The studies have been done on patient-specific human adipose-derived from mesenchymal stem cells (hADSCs) like a series of autologous growth factors and nanofibrous scaffolds (3D culture) will probably have many benefits for regenerative medicine in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a polyvinyl alcohol (PVA) scaffold and a differentiation protocol by adding platelet-rich plasma (PRP) that induces the hADSCs into insulin-producing cells (IPCs). The characteristics of the derived IPCs in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels...
May 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#14
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29096722/pdx1-neurogenin-3-and-mafa-critical-transcription-regulators-for-beta-cell-development-and-regeneration
#15
REVIEW
Yaxi Zhu, Qian Liu, Zhiguang Zhou, Yasuhiro Ikeda
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells...
November 2, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29083510/aetiology-of-type-1-diabetes-physiological-growth-in-children-affects-disease-progression
#16
REVIEW
Oskar Skog, Olle Korsgren
The prevailing view is that type 1 diabetes (T1D) develops as a consequence of a severe decline in β-cell mass resulting from T-cell-mediated autoimmunity; however, progression from islet autoantibody seroconversion to overt diabetes and finally to total loss of C-peptide production occurs in most affected individuals only slowly over many years or even decades. This slow disease progression should be viewed in relation to the total β-cell mass of only 0.2 to 1.5 g in adults without diabetes. Focal lesions of acute pancreatitis with accumulation of leukocytes, often located around the ducts, are frequently observed in people with recent-onset T1D, and most patients display extensive periductal fibrosis, the end stage of inflammation...
April 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29058819/involvement-of-dying-beta-cell-originated-messenger-molecules-in-differentiation-of-pancreatic-mesenchymal-stem-cells-under-glucotoxic-and-glucolipotoxic-conditions
#17
Selda Gezginci-Oktayoglu, Evren Onay-Ucar, Serap Sancar-Bas, Ayse Karatug-Kacar, Emine S N Arda, Sehnaz Bolkent
Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type 2 diabetes mellitus. In this study, pancreatic islet derived mesenchymal stem cells (PI-MSCs) were isolated from adult rats and characterized...
May 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28984038/beta-cell-replacement-strategies-for-diabetes
#18
REVIEW
Timothy J Kieffer, Knut Woltjen, Kenji Osafune, Daisuke Yabe, Nobuya Inagaki
Diabetes is characterized by elevated levels of blood glucose as a result of insufficient production of insulin from loss or dysfunction of pancreatic islet β-cells. Here, we review several approaches to replacing β-cells that were recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human islets can effectively treat diabetes and eliminate the need for insulin injections, supporting research aimed at identifying abundant supplies of cells. Studies showing the feasibility of producing mouse islets in rats support the concept of generating pigs with human pancreas that can serve as donors of human islets, although scientific and ethical challenges remain...
October 6, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28931519/%C3%AE-cell-replacement-in-mice-using-human-type-1-diabetes-nuclear-transfer-embryonic-stem-cells
#19
Lina Sui, Nichole Danzl, Sean R Campbell, Ryan Viola, Damian Williams, Yuan Xing, Yong Wang, Neil Phillips, Greg Poffenberger, Bjarki Johannesson, Jose Oberholzer, Alvin C Powers, Rudolph L Leibel, Xiaojuan Chen, Megan Sykes, Dieter Egli
β-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into β-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature β-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells...
January 2018: Diabetes
https://www.readbyqxmd.com/read/28789815/bioprinting-and-cellular-therapies-for-type-1-diabetes
#20
REVIEW
Dino J Ravnic, Ashley N Leberfinger, Ibrahim T Ozbolat
Type 1 diabetes mellitus is a chronic autoimmune disease that results from the destruction of beta (β) cells in the pancreatic islets, leading to loss of insulin production and resultant hyperglycemia. Recent developments in stem cell biology have generated much excitement for β-cell replacement strategies; β cells are one of many cell types in the complex islet environment and pancreas. In this Opinion, we discuss recent successful attempts to generate β cells and how this can be coupled with bioprinting technologies in order to fabricate pancreas tissues, which holds great potential for type 1 diabetes...
November 2017: Trends in Biotechnology
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