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Special Issue "Patient-Derived Organoids in Personalized Medicine"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 April 2022.

Special Issue Editor

Dr. Zoltán Wiener
E-Mail Website
Guest Editor
Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
Interests: colorectal cancer; pancreas ductal adenocarcinoma; extracellular vesicles; exosomes; organoid; stromal cells

Special Issue Information

Although classical 2D cell cultures have provided a tremendous amount of data on how cancers and other diseases are established, they do not properly model the intra- and interpatient cellular heterogeneity, characteristic for the in vivo situation. In addition, some diseases are difficult to model with mouse systems. As an example, lung cancer is an extremely heterogenous disease with a wide array of mutations; thus, this variance in genetic differences is difficult to capture with mouse models. The 3D organoid technology is a promising tool to solve many of these problems; it captures much of the cellular heterogeneity of the original tissue, is genetically stable, and it represents the complex architecture of the epithelial tissue of origin well. Not surprisingly, this technology has become an invaluable tool in the study of stem cells and their niche, the effect of mutations for diseases, and in finding novel drug combinations for individual cancer patients. Despite the enormous increase in their application and popularity, their standardization is still ongoing, and in many cases maintaining organoids is quite expensive. In this Special Issue, we welcome original articles and reviews about the application of organoids in disease modelling and drug testing, in understanding the development of tissues and organs, and about methodological advancements in organoid technology.

Dr. Zoltán Wiener
Guest Editor

Manuscript Submission Information

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Published Papers (3 papers)

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Research

Article
Fabrication of Hydroxyapatite with Bioglass Nanocomposite for Human Wharton’s-Jelly-Derived Mesenchymal Stem Cell Growing Substrate
Int. J. Mol. Sci. 2021, 22(17), 9637; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179637 - 06 Sep 2021
Cited by 1 | Viewed by 366
Abstract
Recently, composite scaffolding has found many applications in hard tissue engineering due to a number of desirable features. In this present study, hydroxyapatite/bioglass (HAp/BG) nanocomposite scaffolds were prepared in different ratios using a hydrothermal approach. The aim of this research was to evaluate [...] Read more.
Recently, composite scaffolding has found many applications in hard tissue engineering due to a number of desirable features. In this present study, hydroxyapatite/bioglass (HAp/BG) nanocomposite scaffolds were prepared in different ratios using a hydrothermal approach. The aim of this research was to evaluate the adhesion, growth, viability, and osteoblast differentiation behavior of human Wharton’s-jelly-derived mesenchymal stem cells (hWJMSCs) on HAp/BG in vitro as a scaffold for application in bone tissue engineering. Particle size and morphology were investigated by TEM and bioactivity was assessed and proven using SEM analysis with hWJMSCs in contact with the HAp/BG nanocomposite. Viability was evaluated using PrestoBlueTM assay and early osteoblast differentiation and mineralization behaviors were investigated by ALP activity and EDX analysis simultaneously. TEM results showed that the prepared HAp/BG nanocomposite had dimensions of less than 40 nm. The morphology of hWJMSCs showed a fibroblast-like shape, with a clear filopodia structure. The viability of hWJMSCs was highest for the HAp/BG nanocomposite with a 70:30 ratio of HAp to BG (HAp70/BG30). The in vitro biological results confirmed that HAp/BG composite was not cytotoxic. It was also observed that the biological performance of HAp70/BG30 was higher than HAp scaffold alone. In summary, HAp/BG scaffold combined with mesenchymal stem cells showed significant potential for bone repair applications in tissue engineering. Full article
(This article belongs to the Special Issue Patient-Derived Organoids in Personalized Medicine)
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Article
Multicellular Human Cardiac Organoids Transcriptomically Model Distinct Tissue-Level Features of Adult Myocardium
Int. J. Mol. Sci. 2021, 22(16), 8482; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168482 - 06 Aug 2021
Viewed by 468
Abstract
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used for disease modeling and drug cardiotoxicity screening. To this end, we recently developed human cardiac organoids (hCOs) for modeling human myocardium. Here, we perform a transcriptomic analysis of various in vitro hiPSC-CM platforms [...] Read more.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used for disease modeling and drug cardiotoxicity screening. To this end, we recently developed human cardiac organoids (hCOs) for modeling human myocardium. Here, we perform a transcriptomic analysis of various in vitro hiPSC-CM platforms (2D iPSC-CM, 3D iPSC-CM and hCOs) to deduce the strengths and limitations of these in vitro models. We further compared iPSC-CM models to human myocardium samples. Our data show that the 3D in vitro environment of 3D hiPSC-CMs and hCOs stimulates the expression of genes associated with tissue formation. The hCOs demonstrated diverse physiologically relevant cellular functions compared to the hiPSC-CM only models. Including other cardiac cell types within hCOs led to more transcriptomic similarities to adult myocardium. hCOs lack matured cardiomyocytes and immune cells, which limits a complete replication of human adult myocardium. In conclusion, 3D hCOs are transcriptomically similar to myocardium, and future developments of engineered 3D cardiac models would benefit from diversifying cell populations, especially immune cells. Full article
(This article belongs to the Special Issue Patient-Derived Organoids in Personalized Medicine)
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Article
Establishment and Long-Term Expansion of Small Cell Lung Cancer Patient-Derived Tumor Organoids
Int. J. Mol. Sci. 2021, 22(3), 1349; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031349 - 29 Jan 2021
Cited by 3 | Viewed by 797
Abstract
Differential chemo-sensitivity of cancer cells, which is attributed to the cellular heterogeneity and phenotypic variation of cancer cells, is considered to be the main reason for tumor recurrence after chemotherapy. Here, we generated small cell lung cancer patient-derived tumor organoids and subjected them [...] Read more.
Differential chemo-sensitivity of cancer cells, which is attributed to the cellular heterogeneity and phenotypic variation of cancer cells, is considered to be the main reason for tumor recurrence after chemotherapy. Here, we generated small cell lung cancer patient-derived tumor organoids and subjected them to long-term expansion with the addition of WNT3A or R-spondin1. We confirmed that the organoids have similar genetic profiles, molecular characteristics, and morphological architectures to the corresponding patient tumor tissue during and after long-term expansion. Interestingly, the cellular heterogeneity of organoids is reflected in their differential response to cisplatin or etoposide. We propose to utilize the organoids as small cell lung cancer patient avatar models that would be ideal for investigating the mechanisms underlying tumor recurrence after chemotherapy, and would ultimately help to develop personalized medicine. Full article
(This article belongs to the Special Issue Patient-Derived Organoids in Personalized Medicine)
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