Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
Model Systems for Human Disease and Medicine: From Advanced Cell...
share announcement

Model Systems for Human Disease and Medicine: From Advanced Cell and Tissue Culture to In Silico Methods

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Methods".

Deadline for manuscript submissions: 15 May 2024 | Viewed by 7672

Special Issue Editor

Prof. Dr. Jeremy Micah Crook

E-Mail Website
Guest Editor
1. Arto Hardy Family Biomedical Innovation Hub, Chris O'Brien Lifehouse, Camperdown, NSW 2050, Australia
2. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia
3. Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, Fairy Meadow, NSW 2519, Australia
Interests: biomedical engineering; regenerative medicine (incl. stem cells); cancer therapy; medical devices
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Advances in the understanding and treatment of human diseases, whether of unknown (idiopathic) or known origin, are increasingly reliant upon non-animal laboratory-based modelling of cell and tissue biology as well as contributing risk factors. Notwithstanding the many different approaches to modelling, ranging from in vitro-engineered and patient-derived three-dimensional (3D) cell and tissue culture systems (e.g., bioprinted, organoid, cell-on-a-chip) to in silico (computer-based) methods that leverage data from real patients (e.g., genomic, proteomic, metabolomic, pharmacologic, and clinical trials data), an effective model must accurately recapitulate or simulate complex higher-level physiological and pathological aspects of human biology, including therapeutic response in a representative context (i.e., environment). By doing so, biological processes are being identified that are specific to human pathobiology and treatment response, unable to be modelled in a classical animal system. Modelling can be especially important for rare diseases with small patient populations, where both live cell/tissue-based and in silico methods provide scientifically robust frameworks for assessing disease mechanisms and treatment efficacy where it may not be feasible to conduct a clinical trial requiring actual patients only.

This Special Issue will provide a forum to discuss and reflect on the latest progress in laboratory-based modelling for human disease and medicine, ranging from advanced cell and tissue culture to in silico methods, including but not limited to the topics of disease cell and tissue (e.g., developmental, degenerative, cancer, etc.); tissue specific stem cell; native or induced pluripotent stem cell; organoid; cell- and organ-on-a-chip technologies; and cell, gene, and drug therapy. A wide range of contributions are therefore encouraged, including original research reports, review articles, and perspective articles to summarize and reflect on the progress for a specific topic.

We look forward to your contributions.

Prof. Dr. Jeremy Micah Crook
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. Cells is an international peer-reviewed open access semimonthly 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 2700 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

  • modelling
  • human model systems
  • in vitro
  • cells
  • stem cells
  • pluripotent stem cells
  • iPSC
  • tissue
  • organoid
  • organ-on-a-chip
  • cell-on-a-chip
  • in silico
  • disease
  • cancer
  • regenerative medicine
  • diagnostics
  • therapeutics

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

24 pages, 15963 KiB  
Article
Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia
by Ha-Young Kim, Clémentine Charton, Jung Hee Shim, So Young Lim, Jinho Kim, Sejoon Lee, Jung Hun Ohn, Baek Kyu Kim and Chan Yeong Heo
Cells 2024, 13(9), 729; https://doi.org/10.3390/cells13090729 - 23 Apr 2024
Cited by 1 | Viewed by 366
Abstract
Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed [...] Read more.
Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies. Full article
(This article belongs to the Special Issue Model Systems for Human Disease and Medicine: From Advanced Cell and Tissue Culture to In Silico Methods)
►▼ Show Figures

Graphical abstract

17 pages, 4158 KiB  
Article
Protecting Orthopaedic Implants from Infection: Antimicrobial Peptide Mel4 Is Non-Toxic to Bone Cells and Reduces Bacterial Colonisation When Bound to Plasma Ion-Implanted 3D-Printed PAEK Polymers
by Hedi Verena Kruse, Sudip Chakraborty, Renxun Chen, Naresh Kumar, Muhammad Yasir, William T. Lewin, Natalka Suchowerska, Mark D. P. Willcox and David R. McKenzie
Cells 2024, 13(8), 656; https://doi.org/10.3390/cells13080656 - 09 Apr 2024
Viewed by 1021
Abstract
Even with the best infection control protocols in place, the risk of a hospital-acquired infection of the surface of an implanted device remains significant. A bacterial biofilm can form and has the potential to escape the host immune system and develop resistance to [...] Read more.
Even with the best infection control protocols in place, the risk of a hospital-acquired infection of the surface of an implanted device remains significant. A bacterial biofilm can form and has the potential to escape the host immune system and develop resistance to conventional antibiotics, ultimately causing the implant to fail, seriously impacting patient well-being. Here, we demonstrate a 4 log reduction in the infection rate by the common pathogen S. aureus of 3D-printed polyaryl ether ketone (PAEK) polymeric surfaces by covalently binding the antimicrobial peptide Mel4 to the surface using plasma immersion ion implantation (PIII) treatment. The surfaces with added texture created by 3D-printed processes such as fused deposition-modelled polyether ether ketone (PEEK) and selective laser-sintered polyether ketone (PEK) can be equally well protected as conventionally manufactured materials. Unbound Mel4 in solution at relevant concentrations is non-cytotoxic to osteoblastic cell line Saos-2. Mel4 in combination with PIII aids Saos-2 cells to attach to the surface, increasing the adhesion by 88% compared to untreated materials without Mel4. A reduction in mineralisation on the Mel4-containing surfaces relative to surfaces without peptide was found, attributed to the acellular portion of mineral deposition. Full article
(This article belongs to the Special Issue Model Systems for Human Disease and Medicine: From Advanced Cell and Tissue Culture to In Silico Methods)
►▼ Show Figures

Graphical abstract

18 pages, 6862 KiB  
Article
Generation of Fibrotic Liver Organoids Using Hepatocytes, Primary Liver Sinusoidal Endothelial Cells, Hepatic Stellate Cells, and Macrophages
by Yongdae Yoon, Seong Chan Gong, Moon Young Kim, Soon Koo Baik, Ju-Eun Hong, Ki-Jong Rhee, Hoon Ryu and Young Woo Eom
Cells 2023, 12(21), 2514; https://doi.org/10.3390/cells12212514 - 24 Oct 2023
Cited by 1 | Viewed by 2091
Abstract
Liver organoids generated with single or multiple cell types have been used to investigate liver fibrosis development, toxicity, pathogenesis, and drug screening. However, organoid generation is limited by the availability of cells isolated from primary tissues or differentiated from various stem cells. To [...] Read more.
Liver organoids generated with single or multiple cell types have been used to investigate liver fibrosis development, toxicity, pathogenesis, and drug screening. However, organoid generation is limited by the availability of cells isolated from primary tissues or differentiated from various stem cells. To ensure cell availability for organoid formation, we investigated whether liver organoids could be generated with cell-line-based Huh-7 hepatocellular carcinoma cells, macrophages differentiated from THP-1 monocytes, and LX-2 hepatic stellate cells (HSCs) and primary liver sinusoidal endothelial cells (LSECs). In liver organoids, hepatocyte-, LSEC-, macrophage-, and HSC-related gene expression increased relative to that in two-dimensional (2D)-cultured Huh-7/LSEC/THP-1/LX-2 cells without Matrigel. Thioacetamide (TAA) increased α-smooth muscle actin expression in liver organoids but not in 2D-cultured cells, whereas in TAA-treated organoids, the expression of hepatic and LSEC markers decreased and that of macrophage and HSC markers increased. TAA-induced fibrosis was suppressed by treatment with N-acetyl-L-cysteine or tumor-necrosis-factor-stimulated gene 6 protein. The results showed that liver toxicants could induce fibrotic and inflammatory responses in liver organoids comprising Huh-7/LSEC/macrophages/LX-2 cells, resulting in fibrotic liver organoids. We propose that cell-line-based organoids can be used for disease modeling and drug screening to improve liver fibrosis treatment. Full article
(This article belongs to the Special Issue Model Systems for Human Disease and Medicine: From Advanced Cell and Tissue Culture to In Silico Methods)
►▼ Show Figures

Figure 1

19 pages, 4612 KiB  
Article
Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine
by Randy Przybylla, Mathias Krohn, Marie-Luise Sellin, Marcus Frank, Stefan Oswald and Michael Linnebacher
Cells 2023, 12(19), 2371; https://doi.org/10.3390/cells12192371 - 27 Sep 2023
Viewed by 1402
Abstract
The most common in vitro model for absorption, distribution, metabolism, and excretion (ADME) purposes is currently the Caco-2 cell line. However, clear differences in gene and protein expression towards the small intestine and an, at best, fair prediction accuracy of intestinal drug absorption [...] Read more.
The most common in vitro model for absorption, distribution, metabolism, and excretion (ADME) purposes is currently the Caco-2 cell line. However, clear differences in gene and protein expression towards the small intestine and an, at best, fair prediction accuracy of intestinal drug absorption restrict the usefulness of a model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screening of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier-forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, anda higher degree of differentiation was observed in 5/10 cell lines. All lines expressed multiple transporter molecules, with the expression levels in three lines being close to those of small intestinal epithelial cells. Compared with the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In summary, these lines would be better-suited human small intestinal epithelium models for basic and translational research, especially for ADME studies. Full article
(This article belongs to the Special Issue Model Systems for Human Disease and Medicine: From Advanced Cell and Tissue Culture to In Silico Methods)
►▼ Show Figures

Graphical abstract

25 pages, 19162 KiB  
Article
A Novel NCI-H69AR Drug-Resistant Small-Cell Lung Cancer Mini-Tumor Model for Anti-Cancer Treatment Screening
by Alandi van Niekerk, Krzysztof Wrzesinski, Dewald Steyn and Chrisna Gouws
Cells 2023, 12(15), 1980; https://doi.org/10.3390/cells12151980 - 31 Jul 2023
Cited by 1 | Viewed by 1983
Abstract
Small-cell lung cancer is a fast-growing carcinoma with a poor prognosis and a high level of relapse due to multi-drug resistance (MDR). Genetic mutations that lead to the overexpression of efflux transporter proteins can contribute to MDR. In vitro cancer models play a [...] Read more.
Small-cell lung cancer is a fast-growing carcinoma with a poor prognosis and a high level of relapse due to multi-drug resistance (MDR). Genetic mutations that lead to the overexpression of efflux transporter proteins can contribute to MDR. In vitro cancer models play a tremendous role in chemotherapy development and the screening of possible anti-cancer molecules. Low-cost and simple in vitro models are normally used. Traditional two-dimensional (2D) models have numerous shortcomings when considering the physiological resemblance of an in vivo setting. Three-dimensional (3D) models aim to bridge the gap between conventional 2D models and the in vivo setting. Some of the advantages of functional 3D spheroids include better representation of the in vivo physiology and tumor characteristics when compared to traditional 2D cultures. During this study, an NCI-H69AR drug-resistant mini-tumor model (MRP1 hyperexpressive) was developed by making use of a rotating clinostat bioreactor system (ClinoStar®; CelVivo ApS, Odense, Denmark). Spheroid growth and viability were assessed over a 25-day period to determine the ideal experimental period with mature and metabolically stable constructs. The applicability of this model for anti-cancer research was evaluated through treatment with irinotecan, paclitaxel and cisplatin for 96 h, followed by a 96 h recovery period. Parameters measured included planar surface area measurements, estimated glucose consumption, soluble protein content, intracellular adenosine triphosphate levels, extracellular adenylate kinase levels, histology and efflux transporter gene expression. The established functional spheroid model proved viable and stable during the treatment period, with retained relative hyperexpression of the MRP1 efflux transporter gene but increased expression of the P-gp transporter gene compared to the cells cultured in 2D. As expected, treatment with the abovementioned anti-cancer drugs at clinical doses (100 mg/m2 irinotecan, 80 mg/m2 paclitaxel and 75 mg/m2 cisplatin) had minimal impact on the drug-resistant mini-tumors, and the functional spheroid models were able to recover following the removal of treatment. Full article
(This article belongs to the Special Issue Model Systems for Human Disease and Medicine: From Advanced Cell and Tissue Culture to In Silico Methods)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop