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islet 3d

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
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
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...
August 20, 2016: Journal of Pharmacological and Toxicological Methods
A V Mironov, A M Grigoryev, L I Krotova, N N Skaletsky, V K Popov, V 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...
August 20, 2016: Journal of Biomedical Materials Research. Part A
Létitia Jean, Chiu Fan Lee, Peter Hodder, Nick Hawkins, David J Vaux
Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces...
2016: Scientific Reports
Zhilian Yue, Xiao Liu, Patrick T Coates, Gordon G Wallace
PURPOSE OF REVIEW: Rapid advances in bioprinting have attracted the attention of the clinical world. The advent of printable, cytocompatible materials and appropriate hardware provides an unprecedented ability to design and create 3D structures throughout which living cells and bioactive components are strategically distributed. Here, we review those advances and present how they can be used to create new structures for more effective islet cell transplantation. RECENT FINDINGS: There is a need for improvements in the delivery vehicle for transplantable islet cells...
October 2016: Current Opinion in Organ Transplantation
Danielle J Borg, Petra B Welzel, Milauscha Grimmer, Jens Friedrichs, Marc Weigelt, Carmen Wilhelm, Marina Prewitz, Aline Stißel, Angela Hommel, Thomas Kurth, Uwe Freudenberg, Ezio Bonifacio, Carsten Werner
UNLABELLED: Intrahepatic transplantation of allogeneic pancreatic islets offers a promising therapy for type 1 diabetes. However, long-term insulin independency is often not achieved due to severe islet loss shortly after transplantation. To improve islet survival and function, extrahepatic biomaterial-assisted transplantation of pancreatic islets to alternative sites has been suggested. Herein, we present macroporous, star-shaped poly(ethylene glycol) (starPEG)-heparin cryogel scaffolds, covalently modified with adhesion peptides, for the housing of pancreatic islets in three-dimensional (3D) co-culture with adherent mesenchymal stromal cells (MSC) as accessory cells...
October 15, 2016: Acta Biomaterialia
Jessica C Brooks, Katarena I Ford, Dylan H Holder, Mark D Holtan, Christopher J Easley
Employing 3D-printed templates for macro-to-micro interfacing, a passively operated polydimethysiloxane (PDMS) microfluidic device was designed for time-resolved secretion sampling from primary murine islets and epidiymal white adipose tissue explants. Interfacing in similar devices is typically accomplished through manually punched or drilled fluidic reservoirs. We previously introduced the concept of using hand fabricated polymer inserts to template cell culture and sampling reservoirs into PDMS devices, allowing rapid stimulation and sampling of endocrine tissue...
October 21, 2016: Analyst
Erik Bader, Adriana Migliorini, Moritz Gegg, Noah Moruzzi, Jantje Gerdes, Sara S Roscioni, Mostafa Bakhti, Elisabeth Brandl, Martin Irmler, Johannes Beckers, Michaela Aichler, Annette Feuchtinger, Christin Leitzinger, Hans Zischka, Rui Wang-Sattler, Martin Jastroch, Matthias Tschöp, Fausto Machicao, Harald Staiger, Hans-Ulrich Häring, Helena Chmelova, Julie A Chouinard, Nikolay Oskolkov, Olle Korsgren, Stephan Speier, Heiko Lickert
Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of β-cells. Pancreatic β-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential; understanding the mechanisms that underlie this functional heterogeneity might make it possible to develop new regenerative approaches. Here we show that Fltp (also known as Flattop and Cfap126), a Wnt/planar cell polarity (PCP) effector and reporter gene acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature β-cells with distinct molecular, physiological and ultrastructural features...
July 21, 2016: Nature
Andrew Shevchuk, Sergiy Tokar, Sahana Gopal, Jose L Sanchez-Alonso, Andrei I Tarasov, A Catalina Vélez-Ortega, Ciro Chiappini, Patrik Rorsman, Molly M Stevens, Julia Gorelik, Gregory I Frolenkov, David Klenerman, Yuri E Korchev
Scanning ion conductance microscopy (SICM) is a super-resolution live imaging technique that uses a glass nanopipette as an imaging probe to produce three-dimensional (3D) images of cell surface. SICM can be used to analyze cell morphology at nanoscale, follow membrane dynamics, precisely position an imaging nanopipette close to a structure of interest, and use it to obtain ion channel recordings or locally apply stimuli or drugs. Practical implementations of these SICM advantages, however, are often complicated due to the limitations of currently available SICM systems that inherited their design from other scanning probe microscopes in which the scan assembly is placed right above the specimen...
May 24, 2016: Biophysical Journal
Veronica Ibarra, Alyssa A Appel, Mark A Anastasio, Emmanuel C Opara, Eric M Brey
Islet transplantation is currently in clinical use as a treatment for type I diabetes, but donor shortages and long-term immunosuppression limit broad application. Alginate microcapsules coated with poly-l-ornithine can be used to encapsulate islets in an environment that allows diffusion of glucose, insulin, nutrients, and waste products while inhibiting cells and antibodies. While clinical trials are ongoing using islets encapsulated in alginate microbeads, there are concerns in regards to long-term stability...
July 2016: Journal of Biomedical Materials Research. Part A
Giulia Marchioli, Andrea Di Luca, Eelco de Koning, Marten Engelse, Clemens A Van Blitterswijk, Marcel Karperien, Aart A Van Apeldoorn, Lorenzo Moroni
Although regarded as a promising treatment for type 1 diabetes, clinical islet transplantation in the portal vein is still hindered by a low transplantation outcome. Alternative transplantation sites have been proposed, but the survival of extra-hepatically transplanted islets of Langerhans critically depends on quick revascularization after engraftment. This study aims at developing a new 3D scaffold platform that can actively boost vascularization and may find an application for extra-hepatic islet transplantation...
July 2016: Advanced Healthcare Materials
Wael A Eter, Saba Parween, Lieke Joosten, Cathelijne Frielink, Maria Eriksson, Maarten Brom, Ulf Ahlgren, Martin Gotthardt
Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in β-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total β-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate β-cell imaging using radiotracers...
2016: Scientific Reports
Nancy Dekki Shalaly, Massimiliano Ria, Ulrika Johansson, Karin Åvall, Per-Olof Berggren, My Hedhammar
Ex vivo expansion of endocrine cells constitutes an interesting alternative to be able to match the unmet need of transplantable pancreatic islets. However, endocrine cells become fragile once removed from their extracellular matrix (ECM) and typically become senescent and loose insulin expression during conventional 2D culture. Herein we develop a protocol where 3D silk matrices functionalized with ECM-derived motifs are used for generation of insulin-secreting islet-like clusters from mouse and human primary cells...
June 2016: Biomaterials
Wan J Gan, Michael Zavortink, Christine Ludick, Rachel Templin, Robyn Webb, Richard Webb, Wei Ma, Philip Poronnik, Robert G Parton, Herbert Y Gaisano, Annette M Shewan, Peter Thorn
The structural organisation of pancreatic beta cells in the islets of Langerhans is relatively unknown. Here, using 3D two-photon, 3D confocal and 3D block-face serial electron microscopy, we demonstrate a consistent in situ polarisation of beta cells and define three distinct cell-surface domains. An apical domain located at the vascular apogee of beta cells, defined by the location of PAR-3 and ZO-1, delineates an extracellular space into which adjacent beta cells project their primary cilia. A separate lateral domain, is enriched in scribble and Dlg, and colocalises with E-cadherin and GLUT2...
February 26, 2016: Journal of Cell Science
Hajime Matsushima, Tamotsu Kuroki, Tomohiko Adachi, Amane Kitasato, Shinichiro Ono, Takayuki Tanaka, Masataka Hirabaru, Naoki Kuroshima, Takanori Hirayama, Yusuke Sakai, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tatsuya Kin, James Shapiro, Susumu Eguchi
In previous work, we engineered functional cell sheets using bone marrow-derived mesenchymal stem cells (BM-MSCs) to promote islet graft survival. In the present study, we hypothesized that a cell sheet using dermal fibroblasts could be an alternative to MSCs, and then we aimed to evaluate the effects of this cell sheet on the functional viability of human islets. Fibroblast sheets were fabricated using temperature-responsive culture dishes. Human islets were seeded onto fibroblast sheets. The efficacy of the fibroblast sheets was evaluated by dividing islets into three groups: the islets-alone group, the coculture with fibroblasts group, and the islet culture on fibroblast sheet group...
2016: Cell Transplantation
Wenyan Leong, Dong-An Wang
Microsphere technology serves as an efficient and effective platform for cell applications (in vitro cell culture and in vivo cell delivery) due to its mimicry of the 3D native environment, high surface area:volume ratio, and ability to isolate the entrapped cells from the environment. Properties of cell-laden microspheres are determined by the type of application and the cell. While high cell densities are preferable for large-scale therapeutic biomolecule production in vitro, an immunoprotective barrier is most important for allogeneic pancreatic islet transplantation into patients...
November 2015: Trends in Biotechnology
Constantin Ionescu-Tirgoviste, Paul A Gagniuc, Elvira Gubceac, Liliana Mardare, Irinel Popescu, Simona Dima, Manuella Militaru
Islets of Langerhans are fundamental in understanding diabetes. A healthy human pancreas from a donor has been used to asses various islet parameters and their three-dimensional distribution. Here we show that islets are spread gradually from the head up to the tail section of the pancreas in the form of contracted or dilated islet routes. We also report a particular anatomical structure, namely the cluster of islets. Our observations revealed a total of 11 islet clusters which comprise of small islets that surround large blood vessels...
2015: Scientific Reports
Caitlin Cole, Thomas Burgoyne, Annie Lee, Lisa Stehno-Bittel, Gene Zaid
BACKGROUND: Arum palaestinum is a plant commonly found in the Middle East that is ingested as an herbal remedy to fight cancer. However, no studies have examined the direct effect of the plant/plant extract on tumor growth in an animal model. METHODS: Verified prostate cancer cells were plated as 3D spheroids to determine the effect of extract from boiled Arum Palaestinum Boiss roots. In addition, male NU/NU mice (8 weeks old) with xenograft tumors derived from the prostate cancer cell line were treated daily with 1000 mg/kg body weight gavage of the suspension GZ17...
2015: BMC Complementary and Alternative Medicine
Leilani Marty-Santos, Ondine Cleaver
Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell-cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration...
August 2015: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
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