Development of a three‐dimensional in vitro co‐culture model to increase drug selectivity for humans

2020 ◽  
Vol 22 (8) ◽  
pp. 1302-1315
Author(s):  
Sung Bum Park ◽  
Byumseok Koh ◽  
Won Hoon Jung ◽  
Kyoung Jin Choi ◽  
Yoon Ju Na ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Culture Model ◽  
Drug Selectivity

scholarly journals Effects of Ethanol and Acetaldehyde on Tight Junction Integrity: In Vitro Study in a Three Dimensional Intestinal Epithelial Cell Culture Model

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35008 ◽  
Author(s):  
Elhaseen Elamin ◽  
Daisy Jonkers ◽  
Kati Juuti-Uusitalo ◽  
Sven van IJzendoorn ◽  
Freddy Troost ◽  
...  
Keyword(s):  
Cell Culture ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Three Dimensional ◽  
In Vitro Study ◽  
Intestinal Epithelial ◽  
Cell Culture Model ◽  
Epithelial Cell Culture ◽  
Culture Model

scholarly journals An In Vitro Lung System to Assess the Proinflammatory Hazard of Carbon Nanotube Aerosols

2020 ◽  
Vol 21 (15) ◽  
pp. 5335
Author(s):  
Hana Barosova ◽  
Bedia Begum Karakocak ◽  
Dedy Septiadi ◽  
Alke Petri-Fink ◽  
Vicki Stone ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Three Dimensional ◽  
Adverse Outcomes ◽  
Alveolar Epithelial Cells ◽  
Proinflammatory Response ◽  
Multiwalled Carbon ◽  
Alveolar Epithelial ◽  
Culture Model ◽  
Air Liquid Interface

In vitro three-dimensional (3D) lung cell models have been thoroughly investigated in recent years and provide a reliable tool to assess the hazard associated with nanomaterials (NMs) released into the air. In this study, a 3D lung co-culture model was optimized to assess the hazard potential of multiwalled carbon nanotubes (MWCNTs), which is known to provoke inflammation and fibrosis, critical adverse outcomes linked to acute and prolonged NM exposure. The lung co-cultures were exposed to MWCNTs at the air-liquid interface (ALI) using the VITROCELL® Cloud system while considering realistic occupational exposure doses. The co-culture model was composed of three human cell lines: alveolar epithelial cells (A549), fibroblasts (MRC-5), and macrophages (differentiated THP-1). The model was exposed to two types of MWCNTs (Mitsui-7 and Nanocyl) at different concentrations (2–10 μg/cm2) to assess the proinflammatory as well as the profibrotic responses after acute (24 h, one exposure) and prolonged (96 h, repeated exposures) exposure cycles. The results showed that acute or prolonged exposure to different concentrations of the tested MWCNTs did not induce cytotoxicity or apparent profibrotic response; however, suggested the onset of proinflammatory response.

scholarly journals High-Content Image-Based Single-Cell Phenotypic Analysis for the Testicular Toxicity Prediction Induced by Bisphenol A and Its Analogs Bisphenol S, Bisphenol AF, and Tetrabromobisphenol A in a Three-Dimensional Testicular Cell Co-culture Model

2019 ◽  
Vol 173 (2) ◽  
pp. 313-335 ◽  
Author(s):  
Lei Yin ◽  
Jacob Steven Siracusa ◽  
Emily Measel ◽  
Xueling Guan ◽  
Clayton Edenfield ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Three Dimensional ◽  
Testicular Cell ◽  
Phenotypic Analysis ◽  
Bisphenol S ◽  
Cytoskeletal Structure ◽  
Culture Model ◽  
Bisphenol Af

Abstract Emerging data indicate that structural analogs of bisphenol A (BPA) such as bisphenol S (BPS), tetrabromobisphenol A (TBBPA), and bisphenol AF (BPAF) have been introduced into the market as substitutes for BPA. Our previous study compared in vitro testicular toxicity using murine C18-4 spermatogonial cells and found that BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS. Recently, we developed a novel in vitro three-dimensional (3D) testicular cell co-culture model, enabling the classification of reproductive toxic substances. In this study, we applied the testicular cell co-culture model and employed a high-content image (HCA)-based single-cell analysis to further compare the testicular toxicities of BPA and its analogs. We also developed a machine learning (ML)-based HCA pipeline to examine the complex phenotypic changes associated with testicular toxicities. We found dose- and time-dependent changes in a wide spectrum of adverse endpoints, including nuclear morphology, DNA synthesis, DNA damage, and cytoskeletal structure in a single-cell-based analysis. The co-cultured testicular cells were more sensitive than the C18 spermatogonial cells in response to BPA and its analogs. Unlike conventional population-averaged assays, single-cell-based assays not only showed the levels of the averaged population, but also revealed changes in the sub-population. Machine learning-based phenotypic analysis revealed that treatment of BPA and its analogs resulted in the loss of spatial cytoskeletal structure, and an accumulation of M phase cells in a dose- and time-dependent manner. Furthermore, treatment of BPAF-induced multinucleated cells, which were associated with altered DNA damage response and impaired cellular F-actin filaments. Overall, we demonstrated a new and effective means to evaluate multiple toxic endpoints in the testicular co-culture model through the combination of ML and high-content image-based single-cell analysis. This approach provided an in-depth analysis of the multi-dimensional HCA data and provided an unbiased quantitative analysis of the phenotypes of interest.

Author response for "Development of 3D in vitro co‐culture model to increase drug selectivity for humans"

2020 ◽  
Author(s):  
Sung Bum Park ◽  
Byumseok Koh ◽  
Won Hoon Jung ◽  
Kyoung Jin Choi ◽  
Yoon Ju Na ◽  
...  
Keyword(s):  
Author Response ◽  
Culture Model ◽  
Drug Selectivity

Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells

2006 ◽  
Vol 290 (4) ◽  
pp. C1139-C1146 ◽  
Author(s):  
Preeti Malladi ◽  
Yue Xu ◽  
Michael Chiou ◽  
Amato J. Giaccia ◽  
Michael T. Longaker
Keyword(s):  
Oxygen Tension ◽  
Three Dimensional ◽  
Mesenchymal Cells ◽  
Blue Staining ◽  
Great Promise ◽  
Alcian Blue Staining ◽  
Low Oxygen ◽  
Culture Model ◽  
Tgf Β1

Recent studies have demonstrated that adipose-derived mesenchymal cells (AMCs) offer great promise for cell-based therapies because of their ability to differentiate toward bone, cartilage, and fat. Given that cartilage is an avascular tissue and that mesenchymal cells experience hypoxia during prechondrogenic condensation in endochondral ossification, the goal of this study was to understand the influence of oxygen tension on AMC differentiation into bone and cartilage. In vitro chondrogenesis was induced using a three-dimensional micromass culture model supplemented with TGF-β1. Collagen II production and extracellular matrix proteoglycans were assessed with immunohistochemistry and Alcian blue staining, respectively. Strikingly, micromasses differentiated in reduced oxygen tension (2% O2) showed markedly decreased chondrogenesis. Osteogenesis was induced using osteogenic medium supplemented with retinoic acid or vitamin D and was assessed with alkaline phosphatase activity and mineralization. AMCs differentiated in both 21 and 2% O2 environments. However, osteogenesis was severely diminished in a low-oxygen environment. These data demonstrated that hypoxia strongly inhibits in vitro chondrogenesis and osteogenesis in AMCs.

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