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Biomedicines
Special Issues
Drug Screening or Toxicology Research Based on 3D-Cultured Cell Models
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Drug Screening or Toxicology Research Based on 3D-Cultured Cell Models

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 7283

Special Issue Editor

Dr. Dukjin Kang

E-Mail Website
Guest Editor
Biometrology Group, Korea Research Institute of Standards and Science, Daejeon 34113, Republic of Korea
Interests: mass spectrometry; proteomics; metabolomics; 3D cultured cells/organoid; drug screening/toxicology; clinical metrology/certified reference material (CRM)

Special Issue Information

Dear Colleagues,

In this Special Issue, we intend to widen our knowledge about the potential of grafting 3D cultured cell models onto the areas of drug screening and toxicology. From a fundamental hurdle in a two-dimensional (2D) cell culture approach, which is a lack of representation of the microenvironment of in vivo tissue, to date, the demand for the development of three-dimensional (3D) cell culture platforms in both/either drug screening and/or toxicology is gradually magnified. In this regard, it is confidently expected that the similarity of 3D cell cultures to in vivo tissue provides the reliability in drug screening with in-depth understanding of the toxic nature of substances. Herein, we hope that this Special Issue opens up a new promising way to underpin the capability of 3D cultured cell platforms (e.g., spheroids, hanging drop, bioreactors, cell culture scaffolds, and any of the 3D co-cultured fashions) toward either drug screening or toxicology research with a multidisciplinary approach (e.g., multi-omics, bioinformatics, 3D bioimaging, electrophysiological analysis, and so on).

Dr. Dukjin Kang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • three-dimensional cell cultures
  • spheroids
  • scaffolds
  • bioreactors
  • drug screening
  • toxicology

Published Papers (2 papers)

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Research

16 pages, 20738 KiB  
Article
Improving Generation of Cardiac Organoids from Human Pluripotent Stem Cells Using the Aurora Kinase Inhibitor ZM447439
by Su-Jin Lee, Hyeon-A Kim, Sung-Joon Kim and Hyang-Ae Lee
Biomedicines 2021, 9(12), 1952; https://doi.org/10.3390/biomedicines9121952 - 20 Dec 2021
Cited by 7 | Viewed by 2936
Abstract
Drug-induced cardiotoxicity reduces the success rates of drug development. Thus, the limitations of current evaluation methods must be addressed. Human cardiac organoids (hCOs) derived from induced pluripotent stem cells (hiPSCs) are useful as an advanced drug-testing model; they demonstrate similar electrophysiological functionality and [...] Read more.
Drug-induced cardiotoxicity reduces the success rates of drug development. Thus, the limitations of current evaluation methods must be addressed. Human cardiac organoids (hCOs) derived from induced pluripotent stem cells (hiPSCs) are useful as an advanced drug-testing model; they demonstrate similar electrophysiological functionality and drug reactivity as the heart. How-ever, similar to other organoid models, they have immature characteristics compared to adult hearts, and exhibit batch-to-batch variation. As the cell cycle is important for the mesodermal differentiation of stem cells, we examined the effect of ZM447439, an aurora kinase inhibitor that regulates the cell cycle, on cardiogenic differentiation. We determined the optimal concentration and timing of ZM447439 for the differentiation of hCOs from hiPSCs and developed a novel protocol for efficiently and reproducibly generating beating hCOs with improved electrophysiological functionality, contractility, and yield. We validated their maturity through electro-physiological- and image-based functional assays and gene profiling with next-generation sequencing, and then applied these cells to multi-electrode array platforms to monitor the cardio-toxicity of drugs related to cardiac arrhythmia; the results confirmed the drug reactivity of hCOs. These findings may enable determination of the regulatory mechanism of cell cycles underlying the generation of iPSC-derived hCOs, providing a valuable drug testing platform. Full article
(This article belongs to the Special Issue Drug Screening or Toxicology Research Based on 3D-Cultured Cell Models)
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20 pages, 2893 KiB  
Article
In Vitro Miniaturized Tuberculosis Spheroid Model
by Shilpaa Mukundan, Pooja Singh, Aditi Shah, Ranjeet Kumar, Kelly C. O’Neill, Claire L. Carter, David G. Russell, Selvakumar Subbian and Biju Parekkadan
Biomedicines 2021, 9(9), 1209; https://doi.org/10.3390/biomedicines9091209 - 13 Sep 2021
Cited by 6 | Viewed by 3578
Abstract
Tuberculosis (TB) is a public health concern that impacts 10 million people around the world. Current in vitro models are low throughput and/or lack caseation, which impairs drug effectiveness in humans. Here, we report the generation of THP-1 human monocyte/macrophage spheroids housing mycobacteria [...] Read more.
Tuberculosis (TB) is a public health concern that impacts 10 million people around the world. Current in vitro models are low throughput and/or lack caseation, which impairs drug effectiveness in humans. Here, we report the generation of THP-1 human monocyte/macrophage spheroids housing mycobacteria (TB spheroids). These TB spheroids have a central core of dead cells co-localized with mycobacteria and are hypoxic. TB spheroids exhibit higher levels of pro-inflammatory factor TNFα and growth factors G-CSF and VEGF when compared to non-infected control. TB spheroids show high levels of lipid deposition, characterized by MALDI mass spectrometry imaging. TB spheroids infected with strains of differential virulence, Mycobacterium tuberculosis (Mtb) HN878 and CDC1551 vary in response to Isoniazid and Rifampicin. Finally, we adapt the spheroid model to form peripheral blood mononuclear cells (PBMCs) and lung fibroblasts (NHLF) 3D co-cultures. These results pave the way for the development of new strategies for disease modeling and therapeutic discovery. Full article
(This article belongs to the Special Issue Drug Screening or Toxicology Research Based on 3D-Cultured Cell Models)
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