scholarly journals A Modular, Reconfigurable Microfabricated Assembly Platform for Microfluidic Transport and Multitype Cell Culture and Drug Testing

Micromachines ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 2
Author(s):  
Xin Xie ◽  
Sushila Maharjan ◽  
Sanwei Liu ◽  
Yu Shrike Zhang ◽  
Carol Livermore
Keyword(s):  
Cell Culture ◽  
Drug Toxicity ◽  
Drug Testing ◽  
Microelectromechanical Systems ◽  
Single Layer ◽  
Cell Types ◽  
In Vitro Biocompatibility ◽  
Out Of Plane ◽  
Pdms Molding

Modular microfluidics offer the opportunity to combine the precise fluid control, rapid sample processing, low sample and reagent volumes, and relatively lower cost of conventional microfluidics with the flexible reconfigurability needed to accommodate the requirements of target applications such as drug toxicity studies. However, combining the capabilities of fully adaptable modular microelectromechanical systems (MEMS) assembly with the simplicity of conventional microfluidic fabrication remains a challenge. A hybrid polydimethylsiloxane (PDMS)-molding/photolithographic process is demonstrated to rapidly fabricate LEGO®-like modular blocks. The blocks are created with different sizes that interlock via tongue-and-groove joints in the plane and stack via interference fits out of the plane. These miniature strong but reversible connections have a measured resistance to in-plane and out-of-plane forces of up to >6000× and >1000× the weight of the block itself, respectively. The LEGO®-like interference fits enable O-ring-free microfluidic connections that withstand internal fluid pressures of >120 kPa. A single layer of blocks is assembled into LEGO®-like cell culture plates, where the in vitro biocompatibility and drug toxicity to lung epithelial adenocarcinoma cells and hepatocellular carcinoma cells cultured in the modular microwells are measured. A double-layer block structure is then assembled so that a microchannel formed at the interface between layers connects two microwells. Breast tumor cells and hepatocytes cultured in the coupled wells demonstrate interwell migration as well as the simultaneous effects of a single drug on the two cell types.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

scholarly journals Insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinases-2: differential expression and secretion in human kidney tubule cells

2017 ◽  
Vol 312 (2) ◽  
pp. F284-F296 ◽  
Author(s):  
David R. Emlet ◽  
Nuria Pastor-Soler ◽  
Allison Marciszyn ◽  
Xiaoyan Wen ◽  
Hernando Gomez ◽  
...  
Keyword(s):  
Cell Culture ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Human Kidney ◽  
Distal Tubule ◽  
Cell Types ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tubule Cell ◽  
Tubule Cells

We have characterized the expression and secretion of the acute kidney injury (AKI) biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubule cell types yet preferentially secreted by cells of proximal tubule origin. In human kidney tissue, strong staining of IGFBP7 was seen in the luminal brush-border region of a subset of proximal tubule cells, and TIMP-2 stained intracellularly in distal tubules. Additionally, while some tubular colocalization of both biomarkers was identified with the injury markers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, both biomarkers could also be seen alone, suggesting the possibility for differential mechanistic and/or temporal profiles of regulation of these early AKI biomarkers from known markers of injury. Last, an in vitro model of ischemia-reperfusion demonstrated enhancement of secretion of both markers early after reperfusion. This work provides a rationale for further investigation of these markers for their potential role in the pathogenesis of acute kidney injury.

scholarly journals An AC electrothermal self-circulating system with a minimalist process to construct a biomimetic liver lobule model for drug testing

RSC Advances ◽  
2018 ◽  
Vol 8 (65) ◽  
pp. 36987-36998 ◽  
Author(s):  
Shengli Mi ◽  
Baihan Li ◽  
Xiaoman Yi ◽  
Yuanyuan Xu ◽  
Zhichang Du ◽  
...  
Keyword(s):  
Drug Toxicity ◽  
Drug Testing ◽  
Low Cost ◽  
Toxicity Testing ◽  
Liver Lobule ◽  
On Chip

Liver-on-chip, due to its precision and low cost for constructing in vitro models, has tremendous potential for drug toxicity testing and pathological studies.

scholarly journals Fluorescent PSC-Derived Cardiomyocyte Reporter Lines: Generation Approaches and Their Applications in Cardiovascular Medicine

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 402
Author(s):  
Naeramit Sontayananon ◽  
Charles Redwood ◽  
Benjamin Davies ◽  
Katja Gehmlich
Keyword(s):  
Drug Testing ◽  
Cardiac Development ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Specific Cell ◽  
Clinical Safety ◽  
Fluorescent Reporter ◽  
Advantages And Disadvantages ◽  
Attractive Option

Recent advances have made pluripotent stem cell (PSC)-derived cardiomyocytes an attractive option to model both normal and diseased cardiac function at the single-cell level. However, in vitro differentiation yields heterogeneous populations of cardiomyocytes and other cell types, potentially confounding phenotypic analyses. Fluorescent PSC-derived cardiomyocyte reporter systems allow specific cell lineages to be labelled, facilitating cell isolation for downstream applications including drug testing, disease modelling and cardiac regeneration. In this review, the different genetic strategies used to generate such reporter lines are presented with an emphasis on their relative technical advantages and disadvantages. Next, we explore how the fluorescent reporter lines have provided insights into cardiac development and cardiomyocyte physiology. Finally, we discuss how exciting new approaches using PSC-derived cardiomyocyte reporter lines are contributing to progress in cardiac cell therapy with respect to both graft adaptation and clinical safety.

Preliminary testing of silicone-urethane elastomers as substrates in human cell culture

e-Polymers ◽  
2007 ◽  
Vol 7 (1) ◽  
Author(s):  
Malgorzata Lewandowska-Szumieł ◽  
Janusz Kozakiewicz ◽  
Piotr Mrówka ◽  
Agnieszka Jurkowska ◽  
Edyta Sienkiewicz-Łatka ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Culture ◽  
Blood Platelets ◽  
Human Fibroblasts ◽  
Medical Implants ◽  
Tissue Engineering Scaffolds ◽  
Xtt Assay ◽  
In Vitro Biocompatibility ◽  
Different Types

AbstractSilicone-urethanes, polymers combining the characteristics of two widely used biomaterials, i.e. polyurethanes and silicones, are highly valued in many applications, including medical implants. To assess properties of these materials in contact with living cells, a set of different silicone-urethane materials, candidates for tissue engineering scaffolds, was synthesized and characterized. Two different oligomeric siloxane diols: Tegomer-2111 (Teg) and KF-6001 (KF), and two different types of diisocyanate, MDI and IPDI, were used in synthesis. Blood platelets adhesion to surfaces of selected materials showed a higher thrombogenicity of material based on Teg. Human fibroblasts were used in in vitro biocompatibility tests. The viability of cells cultured on silicone-urethanes was tested by XTT assay. Teg-based silicone-urethanes showed a significantly higher biocompatibility than those based on KF. Materials based on MDI compared to IPDI were found to be significantly more favoured by cells, not necessarily due to the type of diisocyanate but maybe also because of the necessity of using potentially toxic catalyst which accompanies the use of IPDI. Our studies indicate that silicone-urethanes are potent materials for tissue engineering products development. On the basis of the observations performed in cell culture, Tegomer- 2111 as oligomeric siloxane diol and MDI as diisocyanate are recommended as starting materials for silicone-urethane scaffolds synthesis.

Patient-derived multicellular prostate cancer spheroids for in vitro cell culture and drug testing

2018 ◽  
Vol 17 (2) ◽  
pp. e366
Author(s):  
J. Linxweiler ◽  
M. Hammer ◽  
A. Pryalukhin ◽  
C. Veith ◽  
K. Junker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Culture ◽  
Drug Testing ◽  
In Vitro Cell Culture ◽  
Cancer Spheroids

scholarly journals In vitro cell culture of patient derived malignant pleural and peritoneal effusions for personalised drug screening

2020 ◽  
Author(s):  
Cheng-Guang Wu ◽  
Francesca Chiovaro ◽  
Alessandra Curioni ◽  
Ruben Casanova ◽  
Alex Soltermann
Keyword(s):  
Cell Culture ◽  
Drug Screening ◽  
Drug Testing ◽  
3D Cell Culture ◽  
Mesothelial Cells ◽  
Screening Methods ◽  
Hanging Drop ◽  
Strong Response ◽  
Sensitivity Testing

Abstract Background Malignant serous effusion (MSE) denotes a manifestation of metastatic disease with typical high concentrations of both cancer and immune cells, making them an ideal resource for in vitro cytologic studies. Hence, the aim of the study was to investigate the features of 2D and 3D MSE culture systems as well as their feasibilities for in vitro drug screening. Methods Pleural and peritoneal effusions from 8 patients were collected and processed for 2D monolayer and 3D hanging drop cell culture into GravityPLUS™ plates. Representative markers for cell components, proliferation rate and tumour classification were investigated by immunohistochemistry, followed by absolute quantification using a digitalised image analysis approach. Further, we implemented another 3D cell culture model based on a low attachment method for in vitro drug sensitivity testing of carboplatin, pemetrexed and pembrolizumab for 5 patients. Results Monolayer cell culture was favourable for the growth of mesothelial cells, while hanging drop culture in GravityPLUS™ plates showed better ability for preserving cancer cells, inducing positive diagnostic markers expression and restraining the growth of mesothelial cells. For in vitro drug testing, MSE from five patients presented various drug sensitivities, and one case showed strong response to PD-1 checkpoint inhibition (pembrolizumab). For some patients, the application of combinatorial drugs had better therapeutic responses compared to monotherapy. Conclusions Digitalised quantification of data offers a better understanding of different MSE culture models. More importantly, the proposed platforms are practical and amenable for performing in vitro chemo-/immunotherapeutic drug testing by using routine cytologic MSE in a personalised manner. Next to cell blocks, our work demonstrates the prognostic and predictive value of cytologic effusion samples.

scholarly journals Infectious clone construction of dengue virus type 2, strain Jamaican 1409, and characterization of a conditional E6 mutation

2006 ◽  
Vol 87 (8) ◽  
pp. 2263-2268 ◽  
Author(s):  
Dennis J. Pierro ◽  
Ma Isabel Salazar ◽  
Barry J. Beaty ◽  
Ken E. Olson
Keyword(s):  
Cell Culture ◽  
Dengue Virus ◽  
Virus Type ◽  
Mammalian Cells ◽  
Infectious Clone ◽  
Cell Types ◽  
Dengue Virus Type 2

A full-length infectious cDNA clone (ic) was constructed from the genome of the dengue virus type 2 (DENV-2) Jamaica83 1409 strain, pBAC1409ic, by using a bacterial artifical chromosome plasmid system. Infectious virus was generated and characterized for growth in cell culture and for infection in Aedes aegypti mosquitoes. During construction, an isoleucine to methionine (Ile→Met) change was found at position 6 in the envelope glycoprotein sequence between low- and high-passage DENV-2 1409 strains. In vitro-transcribed genomic RNA of 1409ic with E6-Ile produced infectious virions following electroporation in mosquito cells, but not mammalian cells, while 1409ic RNA with an E6-Met mutation produced virus in both cell types. Moreover, DENV-2 1409 with the E6-Ile residue produced syncytia in C6/36 cell culture, whereas viruses with E6-Met did not. However, in vitro cell culture-derived growth-curve data and in vivo mosquito-infection rates revealed that none of the analysed DENV-2 strains differed from each other.

In vitro biocompatibility testing of polylactides Part I Proliferation of different cell types

1992 ◽  
Vol 3 (5) ◽  
pp. 365-370 ◽  
Author(s):  
A. van Sliedregt ◽  
A. M. Radder ◽  
K. de Groot ◽  
C. A. van Blitterswijk
Keyword(s):  
Cell Types ◽  
In Vitro Biocompatibility ◽  
Biocompatibility Testing ◽  
Different Cell Types

scholarly journals CurvChip - chip platform for investigating cell responses to curved surface features

2018 ◽  
Vol 4 (1) ◽  
pp. 453-456
Author(s):  
Ralf Kemkemer ◽  
Kerstin Frey ◽  
Alena Fischer ◽  
Rumen Krastev
Keyword(s):  
Low Cost ◽  
Cell Types ◽  
Cell Responses ◽  
Surface Topographies ◽  
Sharp Edges ◽  
Pdms Molding ◽  
The Impact ◽  
Thermal Reflow

AbstractSurface topographies are often discussed as an important parameter influencing basic cell behavior. Whereas most in-vitro studies deal with microstructures with sharp edges, smooth, curved microscale topographies might be more relevant concerning in-vivo situations. Addressing the lack of highly defined surfaces with varying curvature, we present a topography chip system with 3D curved features of varying spacing, curvature radii as well as varying overall dimensions of curved surfaces. The CurvChip is produced by low-cost photolithography with thermal reflow, subsequent (repetitive) PDMS molding and hot embossing. The platform facilitates the systematic invitro investigation of the impact of substrate curvature on cell types like epithelial, endothelial, smooth muscle cells, or stem cells. Such investigations will not only help to further understand the mechanism of curvature sensation but may also contribute to optimize cellmaterial interactions in the field of regenerative medicine.

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