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https://www.readbyqxmd.com/read/28360105/demethylation-of-induced-pluripotent-stem-cells-from-type-1-diabetic-patients-enhances-differentiation-into-functional-pancreatic-%C3%AE-cells
#1
Gohar S Manzar, Eun-Mi Kim, Nicholas Zavazava
Type 1 diabetes (T1D) can be managed by transplanting either the whole pancreas or isolated pancreatic islets. However, cadaveric pancreas is scarcely available for clinical use, limiting this approach. As such, there is a great need to identify alternative sources of clinically usable pancreatic tissues. Here, we used induced pluripotent stem (iPS) cells derived from patients with T1D to generate glucose-responsive, insulin-producing cells (IPCs) via 3D culture. Initially, T1D iPS cells were resistant to differentiation, but transient demethylation treatment significantly enhanced IPC yield...
March 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28347646/allogeneic-islet-cells-implant-on-poly-l-lactide-matrix-to-reduce-hyperglycaemia-in-streptozotocin-induced-diabetic-rat
#2
Siufui Hendrawan, Irawan Yusuf, Mochammad Hatta, Makbul Aman, Ilhamjaya Patellongi, Andreas L Serra, Gatot Lawrence, Ursula Weber, Barlian Sutedja, Hans U Baer
OBJECTIVE: To demonstrate the effects of allogeneic islet cell matrix implants for glycaemic control in rats with induced diabetes. METHOD: Sprague-Dawley rats were used as allogeneic donors of islet cells. Cells were seeded on three-dimensional proprietary poly-(l-lactide) matrices. Animals were rendered diabetic and a week later a matrix seeded with islet cells (IMI group) or a control matrix (placebo group) was implanted in the small bowel mesentery. Blood glucose levels were measured weekly for 12 weeks...
March 1, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28342877/quantitative-visualization-of-synchronized-insulin-secretion-from-3d-cultured-cells
#3
Takahiro Suzuki, Takao Kanamori, Satoshi Inouye
Quantitative visualization of synchronized insulin secretion was performed in an isolated rat pancreatic islet and a spheroid of rat pancreatic beta cell line using a method of video-rate bioluminescence imaging. Video-rate images of insulin secretion from 3D-cultured cells were obtained by expressing the fusion protein of insulin and Gaussia luciferase (Insulin-GLase). A subclonal rat INS-1E cell line stably expressing Insulin-GLase, named iGL, was established and a cluster of iGL cells showed oscillatory insulin secretion that was completely synchronized in response to high glucose...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28303903/a-novel-toolbox-to-investigate-tissue-spatial-organization-applied-to-the-study-of-the-islets-of-langerhans
#4
Hoa Tran Thi Nhu, Rafael Arrojo E Drigo, Per-Olof Berggren, Thomas Boudier
Thanks to the development of new 3D Imaging techniques, volumetric data of thick samples, especially tissues, are commonly available. Several algorithms were proposed to analyze cells or nuclei in tissues, however these tools are limited to two dimensions. Within any given tissue, cells are not likely to be organized randomly and as such have specific patterns of cell-cell interaction forming complex communication networks. In this paper, we propose a new set of tools as an approach to segment and analyze tissues in 3D with single cell resolution...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181140/real-architecture-for-3d-tissue-raft%C3%A2-culture-system-improves-viability-and-maintains-insulin-and-glucagon-production-of-mouse-pancreatic-islet-cells
#5
Gabor J Szebeni, Zsuzsanna Tancos, Liliana Z Feher, Robert Alfoldi, Julianna Kobolak, Andras Dinnyes, Laszlo G Puskas
There is an unmet medical need for the improvement of pancreatic islet maintenance in culture. Due to restricted donor availability it is essential to ameliorate islet viability and graft engraftment. The aim of this study was to compare the standard tissue culture techniques with the advanced Real Architecture For 3D Tissue (RAFT™) culture system in terms of viability and hormone production. Here, we first report that islets embedded in RAFT™ collagen type I advanced tissue culture system maintain their tissue integrity better than in monolayer and suspension cultures...
April 2017: Cytotechnology
https://www.readbyqxmd.com/read/28161954/two-photon-dye-cocktail-for-dual-color-3d-imaging-of-pancreatic-beta-and-alpha-cells-in-live-islets
#6
Bikram Keshari Agrawalla, Hyo Won Lee, Wut-Hmone Phue, Anandhkumar Raju, Jong-Jin Kim, Hwan Myung Kim, Nam-Young Kang, Young-Tae Chang
Insulin-secreting beta cells together with glucagon-producing alpha cells play an essential role in maintaining the optimal blood glucose level in the body, so the development of selective probes for imaging of these cell types in live islets is highly desired. Herein we report the development of a 2-glucosamine-based two-photon fluorescent probe, TP-β, that is suitable for imaging of beta cells in live pancreatic islets from mice. Flow cytometry studies confirmed that TP-β is suitable for isolation of primary beta cells...
February 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28041957/human-pancreatic-%C3%AE-cell-lncrnas-control-cell-specific-regulatory-networks
#7
Ildem Akerman, Zhidong Tu, Anthony Beucher, Delphine M Y Rolando, Claire Sauty-Colace, Marion Benazra, Nikolina Nakic, Jialiang Yang, Huan Wang, Lorenzo Pasquali, Ignasi Moran, Javier Garcia-Hurtado, Natalia Castro, Roser Gonzalez-Franco, Andrew F Stewart, Caroline Bonner, Lorenzo Piemonti, Thierry Berney, Leif Groop, Julie Kerr-Conte, Francois Pattou, Carmen Argmann, Eric Schadt, Philippe Ravassard, Jorge Ferrer
Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/27995203/barofuse-a-novel-pressure-driven-adjustable-throughput-perfusion-system-for-tissue-maintenance-and-assessment
#8
Austin Rountree, Amit Karkamkar, Gamal Khalil, Albert Folch, Daniel L Cook, Ian R Sweet
OBJECTIVES: Microfluidic perfusion systems are used for assessing cell and tissue function while assuring cellular viability. Low perfusate flow rates, desired both for conserving reagents and for extending the number of channels and duration of experiments, conventionally depend on peristaltic pumps to maintain flow yet such pumps are unwieldy and scale poorly for high-throughput applications requiring 16 or more channels. The goal of the study was to develop a scalable multichannel microfluidics system capable of maintaining and assessing kinetic responses of small amounts of tissue to drugs or changes in test conditions...
December 2016: Heliyon
https://www.readbyqxmd.com/read/27990542/3d-templated-fully-automated-microfluidic-input-output-multiplexer-for-endocrine-tissue-culture-and-secretion-sampling
#9
Xiangpeng Li, Jessica C Brooks, Juan Hu, Katarena I Ford, Christopher J Easley
A fully automated, 16-channel microfluidic input/output multiplexer (μMUX) has been developed for interfacing to primary cells and to improve understanding of the dynamics of endocrine tissue function. The device utilizes pressure driven push-up valves for precise manipulation of nutrient input and hormone output dynamics, allowing time resolved interrogation of the cells. The ability to alternate any of the 16 channels from input to output, and vice versa, provides for high experimental flexibility without the need to alter microchannel designs...
January 17, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/27960594/development-of-islet-organoids-from-h9-human-embryonic-stem-cells-in-biomimetic-3d-scaffolds
#10
Weiwei Wang, Sha Jin, Kaiming Ye
Success in the differentiating human embryonic stem cells (hESCs) into insulin-secreting β cells raises new hopes for diabetes treatment. In this work, we demonstrated the feasibility of developing islet organoids from hESCs within biomimetic 3D scaffolds. We showed that such a 3D microenvironment is critical to the generation of pancreatic endoderm and endocrine from hESCs. The organoids formed consisted of pancreatic α, β, δ, and pancreatic polypeptide (PP) cells. A high-level co-expression of PDX1, NKX6...
March 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27956625/clarifying-intact-3d-tissues-on-a-microfluidic-chip-for-high-throughput-structural-analysis
#11
Yih Yang Chen, Pamuditha N Silva, Abdullah Muhammed Syed, Shrey Sindhwani, Jonathan V Rocheleau, Warren C W Chan
On-chip imaging of intact three-dimensional tissues within microfluidic devices is fundamentally hindered by intratissue optical scattering, which impedes their use as tissue models for high-throughput screening assays. Here, we engineered a microfluidic system that preserves and converts tissues into optically transparent structures in less than 1 d, which is 20× faster than current passive clearing approaches. Accelerated clearing was achieved because the microfluidic system enhanced the exchange of interstitial fluids by 567-fold, which increased the rate of removal of optically scattering lipid molecules from the cross-linked tissue...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27941246/lim-domain-binding-1-maintains-the-terminally-differentiated-state-of-pancreatic-%C3%AE-cells
#12
Benjamin N Ediger, Hee-Woong Lim, Christine Juliana, David N Groff, LaQueena T Williams, Giselle Dominguez, Jin-Hua Liu, Brandon L Taylor, Erik R Walp, Vasumathi Kameswaran, Juxiang Yang, Chengyang Liu, Chad S Hunter, Klaus H Kaestner, Ali Naji, Changhong Li, Maike Sander, Roland Stein, Lori Sussel, Kyoung-Jae Won, Catherine Lee May, Doris A Stoffers
The recognition of β cell dedifferentiation in type 2 diabetes raises the translational relevance of mechanisms that direct and maintain β cell identity. LIM domain-binding protein 1 (LDB1) nucleates multimeric transcriptional complexes and establishes promoter-enhancer looping, thereby directing fate assignment and maturation of progenitor populations. Many terminally differentiated endocrine cell types, however, remain enriched for LDB1, but its role is unknown. Here, we have demonstrated a requirement for LDB1 in maintaining the terminally differentiated status of pancreatic β cells...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27895996/label-free-fast-3d-coherent-imaging-reveals-pancreatic-islet-micro-vascularization-and-dynamic-blood-flow
#13
Corinne Berclaz, Daniel Szlag, David Nguyen, Jérôme Extermann, Arno Bouwens, Paul J Marchand, Julia Nilsson, Anja Schmidt-Christensen, Dan Holmberg, Anne Grapin-Botton, Theo Lasser
In diabetes, pancreatic β-cells play a key role. These cells are clustered within structures called islets of Langerhans inside the pancreas and produce insulin, which is directly secreted into the blood stream. The dense vascularization of islets of Langerhans is critical for maintaining a proper regulation of blood glucose homeostasis and is known to be affected from the early stage of diabetes. The deep localization of these islets inside the pancreas in the abdominal cavity renders their in vivo visualization a challenging task...
November 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27889104/three-dimensional-reconstruction-of-the-embryonic-pancreas-in-the-grass-snake-natrix-natrix-l-lepidosauria-serpentes-based-on-histological-studies
#14
Magdalena Kowalska, Mateusz Hermyt, Weronika Rupik
The aim of this study was to evaluate two research hypotheses: H0-the embryonic pancreas in grass snakes develops in the same manner as in all previously investigated amniotes (from three buds) and its topographical localization within the adult body has no relation to its development; H1-the pancreas develops in a different manner and is related to the different topography of internal organs in snakes. For the evaluation of these hypotheses we used histological methods and three-dimensional (3D) reconstructions of the position of the pancreatic buds and surrounding organs at particular developmental stages and of the final position and shape of the pancreatic gland...
November 11, 2016: Zoology: Analysis of Complex Systems, ZACS
https://www.readbyqxmd.com/read/27802569/modeling-spatial-distribution-of-oxygen-in-3d-culture-of-islet-beta-cells
#15
John McReynolds, Yu Wen, Xiaofei Li, Jianjun Guan, Sha Jin
Three-dimensional (3D) scaffold culture of pancreatic β-cell has been proven to be able to better mimic physiological conditions in the body. However, one critical issue with culturing pancreatic β-cells is that β-cells consume large amounts of oxygen, and hence insufficient oxygen supply in the culture leads to loss of β-cell mass and functions. This becomes more significant when cells are cultured in a 3D scaffold. In this study, in order to understand the effect of oxygen tension inside a cell-laden collagen culture on β-cell proliferation, a culture model with encapsulation of an oxygen-generator was established...
November 1, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27796159/imaging-of-hydrogel-microsphere-structure-and-foreign-body-response-based-on-endogenous-x-ray-phase-contrast
#16
Alyssa A Appel, Veronica Ibarra, Sami I Somo, Jeffery C Larson, Alfred B Garson, Huifeng Guan, John Patrick McQuilling, Zhong Zhong, Mark A Anastasio, Emmanuel C Opara, Eric M Brey
Transplantation of functional islets encapsulated in stable biomaterials has the potential to cure Type I diabetes. However, the success of these materials requires the ability to quantitatively evaluate their stability. Imaging techniques that enable monitoring of biomaterial performance are critical to further development in the field. X-ray phase-contrast (XPC) imaging is an emerging class of X-ray techniques that have shown significant promise for imaging biomaterial and soft tissue structures. In this study, XPC imaging techniques are shown to enable three dimensional (3D) imaging and evaluation of islet volume, alginate hydrogel structure, and local soft tissue features ex vivo...
November 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27731367/islet-like-organoids-derived-from-human-pluripotent-stem-cells-efficiently-function-in-the-glucose-responsiveness-in-vitro-and-in-vivo
#17
Youngjin Kim, Hyeongseok Kim, Ung Hyun Ko, Youjin Oh, Ajin Lim, Jong-Woo Sohn, Jennifer H Shin, Hail Kim, Yong-Mahn Han
Insulin secretion is elaborately modulated in pancreatic ß cells within islets of three-dimensional (3D) structures. Using human pluripotent stem cells (hPSCs) to develop islet-like structures with insulin-producing ß cells for the treatment of diabetes is challenging. Here, we report that pancreatic islet-like clusters derived from hESCs are functionally capable of glucose-responsive insulin secretion as well as therapeutic effects. Pancreatic hormone-expressing endocrine cells (ECs) were differentiated from hESCs using a step-wise protocol...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27713548/intra-islet-lesions-and-lobular-variations-in-%C3%AE-cell-mass-expansion-in-ob-ob-mice-revealed-by-3d-imaging-of-intact-pancreas
#18
Saba Parween, Elena Kostromina, Christoffer Nord, Maria Eriksson, Per Lindström, Ulf Ahlgren
The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age...
October 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27554916/a-simple-reliable-method-for-high-throughput-screening-for-diabetes-drugs-using-3d-%C3%AE-cell-spheroids
#19
Jesal Amin, Karthik Ramachandran, S Janette Williams, Annie Lee, Lesya Novikova, Lisa Stehno-Bittel
Early screens for new diabetes drugs rely on monolayers of β-cells, which are known to be poor predictors of the in vivo response. Previously, we developed a method to create uniform islet spheroids from freshly-dispersed human donor tissue for drug screening. While the human engineered islets worked well to reduce donor-to-donor variability, it is difficult and expensive to obtain sufficient high-quality human islets for drug testing. Thus, this study utilized a genetically-modified β-cell culture line (INS-1832/13) in 2D and as 3D spheroids and compared the results to human islet tissue formed into spheroids using a high-throughput 384-well format...
November 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27543196/3d-printing-of-plga-scaffolds-for-tissue-engineering
#20
Anton V Mironov, Aleksey M Grigoryev, Larisa I Krotova, Nikolaj N Skaletsky, Vladimir K Popov, Viktor I Sevastianov
We proposed a novel method of generation of bioresorbable polymeric scaffolds with specified architectonics for tissue engineering using extrusion three-dimensional (3D) printing with solutions of polylactoglycolide in tetraglycol with their subsequent solidifying in aqueous medium. On the basis of 3D computer models, we obtained the matrix structures with interconnected system of pores ranging in size from 0.5 to 500 µm. The results of in vitro studies using cultures of line NIH 3Т3 mouse fibroblasts, floating islet cultures of newborn rabbit pancreas, and mesenchymal stem cells of human adipose tissue demonstrated the absence of cytotoxicity and good adhesive properties of scaffolds in regard to the cell cultures chosen...
January 2017: Journal of Biomedical Materials Research. Part A
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