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Organoids: The New 3D-Frontier to Model Different Diseases In Vitro

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

Deadline for manuscript submissions: closed (25 August 2023) | Viewed by 25796

Special Issue Editors

Department of Biomedical and Clinical Sciences, Università di Milano, 20157 Milano, Italy
Interests: magnesium; organoids; iPS; mesenchymal stem cells; endothelium
Special Issues, Collections and Topics in MDPI journals
Department of Biomedical and Clinical Sciences, Università di Milano, 20157 Milano, Italy
Interests: molecular and cellular biology;osteogenic and miogenic differentiation; magnesium; microgravity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Organoids are miniaturized replicates of human organs that recreate their architecture and physiology. They are generated from patient biopsy samples or from induced pluripotent stem cells and provide an unprecedented tool to model organogenesis and human diseases. Organoids have been used to study genetic disorders and infectious diseases as well as for drug screening. They represent a valid alternative or complement to animal models, because it is complex to extrapolate results from model systems to humans. On the other hand, it is well known that biological processes specific to the human body cannot be modelled in other animals. Moreover, organoids might become a useful tool in the perspective of personalized medicine and therapy.

This Special Issue calls for papers presenting the implementation of organoid technology and offering novel insights into organogenesis, as well as into the pathophysiology of diseases.

Dr. Alessandra Cazzaniga
Dr. Sara Castiglioni
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • organoids
  • organoid technology
  • brain
  • gut
  • liver
  • organogenesis
  • vascularization
  • metabolism
  • inflammation
  • stress
  • cancer

Published Papers (12 papers)

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Research

Jump to: Review

16 pages, 2985 KiB  
Article
Cerebral Organoid Arrays for Batch Phenotypic Analysis in Sections and Three Dimensions
by Juan Chen, Haihua Ma, Zhiyu Deng, Qingming Luo, Hui Gong, Ben Long and Xiangning Li
Int. J. Mol. Sci. 2023, 24(18), 13903; https://doi.org/10.3390/ijms241813903 - 09 Sep 2023
Viewed by 1078
Abstract
Organoids can recapitulate human-specific phenotypes and functions in vivo and have great potential for research in development, disease modeling, and drug screening. Due to the inherent variability among organoids, experiments often require a large sample size. Embedding, staining, and imaging each organoid individually [...] Read more.
Organoids can recapitulate human-specific phenotypes and functions in vivo and have great potential for research in development, disease modeling, and drug screening. Due to the inherent variability among organoids, experiments often require a large sample size. Embedding, staining, and imaging each organoid individually require a lot of reagents and time. Hence, there is an urgent need for fast and efficient methods for analyzing the phenotypic changes in organoids in batches. Here, we provide a comprehensive strategy for array embedding, staining, and imaging of cerebral organoids in both agarose sections and in 3D to analyze the spatial distribution of biomarkers in organoids in situ. We constructed several disease models, particularly an aging model, as examples to demonstrate our strategy for the investigation of the phenotypic analysis of organoids. We fabricated an array mold to produce agarose support with microwells, which hold organoids in place for live/dead imaging. We performed staining and imaging of sectioned organoids embedded in agarose and 3D imaging to examine phenotypic changes in organoids using fluorescence micro-optical sectioning tomography (fMOST) and whole-mount immunostaining. Parallel studies of organoids in arrays using the same staining and imaging parameters enabled easy and reliable comparison among different groups. We were able to track all the data points obtained from every organoid in an embedded array. This strategy could help us study the phenotypic changes in organoids in disease models and drug screening. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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16 pages, 9432 KiB  
Article
Ascites-Derived Organoids to Depict Platinum Resistance in Gynaecological Serous Carcinomas
by Andrea Estrella Arias-Diaz, Miriam Ferreiro-Pantin, Jorge Barbazan, Edurne Perez-Beliz, Juan Ruiz-Bañobre, Carlos Casas-Arozamena, Laura Muinelo-Romay, Rafael Lopez-Lopez, Ana Vilar, Teresa Curiel and Miguel Abal
Int. J. Mol. Sci. 2023, 24(17), 13208; https://doi.org/10.3390/ijms241713208 - 25 Aug 2023
Cited by 1 | Viewed by 1361
Abstract
Gynaecological serous carcinomas (GSCs) constitute a distinctive entity among female tumours characterised by a very poor prognosis. In addition to late-stage diagnosis and a high rate of recurrent disease associated with massive peritoneal carcinomatosis, the systematic acquisition of resistance to first-line chemotherapy based [...] Read more.
Gynaecological serous carcinomas (GSCs) constitute a distinctive entity among female tumours characterised by a very poor prognosis. In addition to late-stage diagnosis and a high rate of recurrent disease associated with massive peritoneal carcinomatosis, the systematic acquisition of resistance to first-line chemotherapy based on platinum determines the unfavourable outcome of GSC patients. To explore the molecular mechanisms associated with platinum resistance, we generated patient-derived organoids (PDOs) from liquid biopsies of GSC patients. PDOs are emerging as a relevant preclinical model system to assist in clinical decision making, mainly from tumoural tissue and particularly for personalised therapeutic options. To approach platinum resistance in a GSC context, proficient PDOs were generated from the ascitic fluid of ovarian, primary peritoneal and uterine serous carcinoma patients in platinum-sensitive and platinum-resistant clinical settings from the uterine aspirate of a uterine serous carcinoma patient, and we also induced platinum resistance in vitro in a representative platinum-sensitive PDO. Histological and immunofluorescent characterisation of these ascites-derived organoids showed resemblance to the corresponding original tumours, and assessment of platinum sensitivity in these preclinical models replicated the clinical setting of the corresponding GSC patients. Differential gene expression profiling of a panel of 770 genes representing major canonical cancer pathways, comparing platinum-sensitive and platinum-resistant PDOs, revealed cellular response to DNA damage stimulus as the principal biological process associated with the acquisition of resistance to the first-line therapy for GSC. Additionally, candidate genes involved in regulation of cell adhesion, cell cycles, and transcription emerged from this proof-of-concept study. In conclusion, we describe the generation of PDOs from liquid biopsies in the context of gynaecological serous carcinomas to explore the molecular determinants of platinum resistance. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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19 pages, 3374 KiB  
Article
Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis
by Gema Gomez-Mariano, Sara Perez-Luz, Sheila Ramos-Del Saz, Nerea Matamala, Esther Hernandez-SanMiguel, Marta Fernandez-Prieto, Sara Gil-Martin, Iago Justo, Alberto Marcacuzco and Beatriz Martinez-Delgado
Int. J. Mol. Sci. 2023, 24(16), 12645; https://doi.org/10.3390/ijms241612645 - 10 Aug 2023
Viewed by 1346
Abstract
Acid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease type A (NPA), type B (NPB) and type A/B (NPA/B), is a rare lysosomal storage disease characterized by progressive accumulation of sphingomyelin (SM) in the liver, lungs, bone marrow and, in severe cases, neurons. A disease [...] Read more.
Acid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease type A (NPA), type B (NPB) and type A/B (NPA/B), is a rare lysosomal storage disease characterized by progressive accumulation of sphingomyelin (SM) in the liver, lungs, bone marrow and, in severe cases, neurons. A disease model was established by generating liver organoids from a NPB patient carrying the p.Arg610del variant in the SMPD1 gene. Liver organoids were characterized by transcriptomic and lipidomic analysis. We observed altered lipid homeostasis in the patient-derived organoids showing the predictable increase in sphingomyelin (SM), together with cholesterol esters (CE) and triacylglycerides (TAG), and a reduction in phosphatidylcholine (PC) and cardiolipins (CL). Analysis of lysosomal gene expression pointed to 24 downregulated genes, including SMPD1, and 26 upregulated genes that reflect the lysosomal stress typical of the disease. Altered genes revealed reduced expression of enzymes that could be involved in the accumulation in the hepatocytes of sphyngoglycolipids and glycoproteins, as well as upregulated genes coding for different glycosidases and cathepsins. Lipidic and transcriptome changes support the use of hepatic organoids as ideal models for ASMD investigation. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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14 pages, 1503 KiB  
Communication
Theratyping of the Rare CFTR Genotype A559T in Rectal Organoids and Nasal Cells Reveals a Relevant Response to Elexacaftor (VX-445) and Tezacaftor (VX-661) Combination
by Karina Kleinfelder, Valeria Rachela Villella, Anca Manuela Hristodor, Carlo Laudanna, Giuseppe Castaldo, Felice Amato, Paola Melotti and Claudio Sorio
Int. J. Mol. Sci. 2023, 24(12), 10358; https://doi.org/10.3390/ijms241210358 - 19 Jun 2023
Cited by 3 | Viewed by 1210
Abstract
Despite the promising results of new CFTR targeting drugs designed for the recovery of F508del- and class III variants activity, none of them have been approved for individuals with selected rare mutations, because uncharacterized CFTR variants lack information associated with the ability of [...] Read more.
Despite the promising results of new CFTR targeting drugs designed for the recovery of F508del- and class III variants activity, none of them have been approved for individuals with selected rare mutations, because uncharacterized CFTR variants lack information associated with the ability of these compounds in recovering their molecular defects. Here we used both rectal organoids (colonoids) and primary nasal brushed cells (hNEC) derived from a CF patient homozygous for A559T (c.1675G>A) variant to evaluate the responsiveness of this pathogenic variant to available CFTR targeted drugs that include VX-770, VX-809, VX-661 and VX-661 combined with VX-445. A559T is a rare mutation, found in African-Americans people with CF (PwCF) with only 85 patients registered in the CFTR2 database. At present, there is no treatment approved by FDA (U.S. Food and Drug Administration) for this genotype. Short-circuit current (Isc) measurements indicate that A559T-CFTR presents a minimal function. The acute addition of VX-770 following CFTR activation by forskolin had no significant increment of baseline level of anion transport in both colonoids and nasal cells. However, the combined treatment, VX-661-VX-445, significantly increases the chloride secretion in A559T-colonoids monolayers and hNEC, reaching approximately 10% of WT-CFTR function. These results were confirmed by forskolin-induced swelling assay and by western blotting in rectal organoids. Overall, our data show a relevant response to VX-661-VX-445 in rectal organoids and hNEC with CFTR genotype A559T/A559T. This could provide a strong rationale for treating patients carrying this variant with VX-661-VX-445-VX-770 combination. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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16 pages, 9022 KiB  
Article
Production of Mare Chorionic Girdle Organoids That Secrete Equine Chorionic Gonadotropin
by Riley E. Thompson, Mindy A. Meyers, Jennifer Palmer, D. N. Rao Veeramachaneni, Christianne Magee, Amanda M. de Mestre, Douglas F. Antczak and Fiona K. Hollinshead
Int. J. Mol. Sci. 2023, 24(11), 9538; https://doi.org/10.3390/ijms24119538 - 31 May 2023
Cited by 2 | Viewed by 1387
Abstract
The equine chorionic girdle is comprised of specialized invasive trophoblast cells that begin formation approximately 25 days after ovulation (day 0) and invade the endometrium to become endometrial cups. These specialized trophoblast cells transition from uninucleate to differentiated binucleate trophoblast cells that secrete [...] Read more.
The equine chorionic girdle is comprised of specialized invasive trophoblast cells that begin formation approximately 25 days after ovulation (day 0) and invade the endometrium to become endometrial cups. These specialized trophoblast cells transition from uninucleate to differentiated binucleate trophoblast cells that secrete the glycoprotein hormone equine chorionic gonadotropin (eCG; formerly known as pregnant mare serum gonadotropin or PMSG). This eCG has LH-like activity in the horse but variable LH- and FSH-like activity in other species and has been utilized for these properties both in vivo and in vitro. To produce eCG commercially, large volumes of whole blood must be collected from pregnant mares, which negatively impacts equine welfare due to repeated blood collections and the birth of an unwanted foal. Attempts to produce eCG in vitro using long-term culture of chorionic girdle explants have not been successful beyond 180 days, with peak eCG production at 30 days of culture. Organoids are three-dimensional cell clusters that self-organize and can remain genetically and phenotypically stable throughout long-term culture (i.e., months). Human trophoblast organoids have been reported to successfully produce human chorionic gonadotropin (hCG) and proliferate long-term (>1 year). The objective of this study was to evaluate whether organoids derived from equine chorionic girdle maintain physiological functionality. Here we show generation of chorionic girdle organoids for the first time and demonstrate in vitro production of eCG for up to 6 weeks in culture. Therefore, equine chorionic girdle organoids provide a physiologically representative 3D in vitro model for chorionic girdle development of early equine pregnancy. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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14 pages, 1696 KiB  
Article
Airway and Lung Organoids from Human-Induced Pluripotent Stem Cells Can Be Used to Assess CFTR Conductance
by Anna Demchenko, Ekaterina Kondrateva, Vyacheslav Tabakov, Anna Efremova, Diana Salikhova, Tatiana Bukharova, Dmitry Goldshtein, Maxim Balyasin, Natalia Bulatenko, Elena Amelina, Alexander Lavrov and Svetlana Smirnikhina
Int. J. Mol. Sci. 2023, 24(7), 6293; https://doi.org/10.3390/ijms24076293 - 27 Mar 2023
Cited by 2 | Viewed by 2002
Abstract
Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell–cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining organoids. In this article, we [...] Read more.
Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell–cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining organoids. In this article, we describe a step-by-step protocol for differentiating hiPSCs into airway and lung organoids. We obtained airway and lung organoids from a healthy donor and from five donors with cystic fibrosis. Analysis of the cellular composition of airway and lung organoids showed that airway organoids contain proximal lung epithelial cells, while lung organoids contain both proximal and distal lung epithelial cells. Forskolin-induced swelling of organoids derived from a healthy donor showed that lung organoids, as well as airway organoids, contain functional epithelial cells and swell after 24 h exposure to forskolin, which makes it a suitable model for analyzing the cystic fibrosis transmembrane conductance regulator (CFTR) channel conductance in vitro. Thus, our results demonstrate the feasibility of generating and characterizing airway and lung organoids from hiPSCs, which can be used for a variety of future applications. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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15 pages, 1950 KiB  
Article
A Novel Preclinical In Vitro 3D Model of Oral Carcinogenesis for Biomarker Discovery and Drug Testing
by Ravi Teja Chitturi Suryaprakash, Kate Shearston, Camile S. Farah, Simon A. Fox, Muhammad Munir Iqbal, Ulrich Kadolsky, Xiao Zhong, Alka Saxena and Omar Kujan
Int. J. Mol. Sci. 2023, 24(4), 4096; https://doi.org/10.3390/ijms24044096 - 17 Feb 2023
Cited by 4 | Viewed by 2573
Abstract
This study aimed to develop an in vitro three-dimensional (3D) cell culture model of oral carcinogenesis for the rapid, scalable testing of chemotherapeutic agents. Spheroids of normal (HOK) and dysplastic (DOK) human oral keratinocytes were cultured and treated with 4-nitroquinoline-1-oxide (4NQO). A 3D [...] Read more.
This study aimed to develop an in vitro three-dimensional (3D) cell culture model of oral carcinogenesis for the rapid, scalable testing of chemotherapeutic agents. Spheroids of normal (HOK) and dysplastic (DOK) human oral keratinocytes were cultured and treated with 4-nitroquinoline-1-oxide (4NQO). A 3D invasion assay using Matrigel was performed to validate the model. RNA was extracted and subjected to transcriptomic analysis to validate the model and assess carcinogen-induced changes. The VEGF inhibitors pazopanib and lenvatinib were tested in the model and were validated by a 3D invasion assay, which demonstrated that changes induced by the carcinogen in spheroids were consistent with a malignant phenotype. Further validation was obtained by bioinformatic analyses, which showed the enrichment of pathways associated with hallmarks of cancer and VEGF signalling. Overexpression of common genes associated with tobacco-induced oral squamous cell carcinoma (OSCC), such as MMP1, MMP3, MMP9, YAP1, CYP1A1, and CYP1B1, was also observed. Pazopanib and lenvatinib inhibited the invasion of transformed spheroids. In summary, we successfully established a 3D spheroid model of oral carcinogenesis for biomarker discovery and drug testing. This model is a validated preclinical model for OSCC development and would be suitable for testing a range of chemotherapeutic agents. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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15 pages, 2739 KiB  
Article
Neutralising Effects of Different Antibodies on Clostridioides difficile Toxins TcdA and TcdB in a Translational Approach
by Georg Csukovich, Nina Kramer, Barbara Pratscher, Ivana Gotic, Patricia Freund, Rainer Hahn, Gottfried Himmler, Sabine Brandt and Iwan Anton Burgener
Int. J. Mol. Sci. 2023, 24(4), 3867; https://doi.org/10.3390/ijms24043867 - 15 Feb 2023
Cited by 2 | Viewed by 1785
Abstract
Given the high prevalence of intestinal disease in humans and animals, there is a strong need for clinically relevant models recapitulating gastrointestinal systems, ideally replacing in vivo models in accordance with the principles of the 3R. We established a canine organoid system and [...] Read more.
Given the high prevalence of intestinal disease in humans and animals, there is a strong need for clinically relevant models recapitulating gastrointestinal systems, ideally replacing in vivo models in accordance with the principles of the 3R. We established a canine organoid system and analysed the neutralising effects of recombinant versus natural antibodies on Clostridioides difficile toxins A and B in this in vitro system. Sulforhodamine B cytotoxicity assays in 2D and FITC-dextran barrier integrity assays on basal-out and apical-out organoids revealed that recombinant, but not natural antibodies, effectively neutralised C. difficile toxins. Our findings emphasise that canine intestinal organoids can be used to test different components and suggest that they can be further refined to also mirror complex interactions between the intestinal epithelium and other cells. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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17 pages, 7211 KiB  
Article
A Microwell-Based Intestinal Organoid-Macrophage Co-Culture System to Study Intestinal Inflammation
by Panagiota Kakni, Roman Truckenmüller, Pamela Habibović, Martijn van Griensven and Stefan Giselbrecht
Int. J. Mol. Sci. 2022, 23(23), 15364; https://doi.org/10.3390/ijms232315364 - 06 Dec 2022
Cited by 8 | Viewed by 3185
Abstract
The mammalian intestinal epithelium contains more immune cells than any other tissue, and this is largely because of its constant exposure to pathogens. Macrophages are crucial for maintaining intestinal homeostasis, but they also play a central role in chronic pathologies of the digestive [...] Read more.
The mammalian intestinal epithelium contains more immune cells than any other tissue, and this is largely because of its constant exposure to pathogens. Macrophages are crucial for maintaining intestinal homeostasis, but they also play a central role in chronic pathologies of the digestive system. We developed a versatile microwell-based intestinal organoid-macrophage co-culture system that enables us to recapitulate features of intestinal inflammation. This microwell-based platform facilitates the controlled positioning of cells in different configurations, continuous in situ monitoring of cell interactions, and high-throughput downstream applications. Using this novel system, we compared the inflammatory response when intestinal organoids were co-cultured with macrophages versus when intestinal organoids were treated with the pro-inflammatory cytokine TNF-α. Furthermore, we demonstrated that the tissue-specific response differs according to the physical distance between the organoids and the macrophages and that the intestinal organoids show an immunomodulatory competence. Our novel microwell-based intestinal organoid model incorporating acellular and cellular components of the immune system can pave the way to unravel unknown mechanisms related to intestinal homeostasis and disorders. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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Review

Jump to: Research

14 pages, 1890 KiB  
Review
Application of Human Brain Organoids—Opportunities and Challenges in Modeling Human Brain Development and Neurodevelopmental Diseases
by Soo-hyun Kim and Mi-Yoon Chang
Int. J. Mol. Sci. 2023, 24(15), 12528; https://doi.org/10.3390/ijms241512528 - 07 Aug 2023
Cited by 4 | Viewed by 3534
Abstract
Brain organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that reflect early brain organization. These organoids contain different cell types, including neurons and glia, similar to those found in the human brain. Human brain organoids provide unique opportunities to [...] Read more.
Brain organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that reflect early brain organization. These organoids contain different cell types, including neurons and glia, similar to those found in the human brain. Human brain organoids provide unique opportunities to model features of human brain development that are not well-reflected in animal models. Compared with traditional cell cultures and animal models, brain organoids offer a more accurate representation of human brain development and function, rendering them suitable models for neurodevelopmental diseases. In particular, brain organoids derived from patients’ cells have enabled researchers to study diseases at different stages and gain a better understanding of disease mechanisms. Multi-brain regional assembloids allow for the investigation of interactions between distinct brain regions while achieving a higher level of consistency in molecular and functional characterization. Although organoids possess promising features, their usefulness is limited by several unresolved constraints, including cellular stress, hypoxia, necrosis, a lack of high-fidelity cell types, limited maturation, and circuit formation. In this review, we discuss studies to overcome the natural limitations of brain organoids, emphasizing the importance of combinations of all neural cell types, such as glia (astrocyte, oligodendrocytes, and microglia) and vascular cells. Additionally, considering the similarity of organoids to the developing brain, regionally patterned brain organoid-derived neural stem cells (NSCs) could serve as a scalable source for cell replacement therapy. We highlight the potential application of brain organoid-derived cells in disease cell therapy within this field. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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26 pages, 2076 KiB  
Review
Glioblastoma Microenvironment and Invasiveness: New Insights and Therapeutic Targets
by José Ignacio Erices, Carolina Bizama, Ignacio Niechi, Daniel Uribe, Arnaldo Rosales, Karen Fabres, Giovanna Navarro-Martínez, Ángelo Torres, Rody San Martín, Juan Carlos Roa and Claudia Quezada-Monrás
Int. J. Mol. Sci. 2023, 24(8), 7047; https://doi.org/10.3390/ijms24087047 - 11 Apr 2023
Cited by 14 | Viewed by 3118
Abstract
Glioblastoma (GBM) is the most common and malignant primary brain cancer in adults. Without treatment the mean patient survival is approximately 6 months, which can be extended to 15 months with the use of multimodal therapies. The low effectiveness of GBM therapies is [...] Read more.
Glioblastoma (GBM) is the most common and malignant primary brain cancer in adults. Without treatment the mean patient survival is approximately 6 months, which can be extended to 15 months with the use of multimodal therapies. The low effectiveness of GBM therapies is mainly due to the tumor infiltration into the healthy brain tissue, which depends on GBM cells’ interaction with the tumor microenvironment (TME). The interaction of GBM cells with the TME involves cellular components such as stem-like cells, glia, endothelial cells, and non-cellular components such as the extracellular matrix, enhanced hypoxia, and soluble factors such as adenosine, which promote GBM’s invasiveness. However, here we highlight the role of 3D patient-derived glioblastoma organoids cultures as a new platform for study of the modeling of TME and invasiveness. In this review, the mechanisms involved in GBM-microenvironment interaction are described and discussed, proposing potential prognosis biomarkers and new therapeutic targets. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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17 pages, 608 KiB  
Review
Developmental Toxicity Studies: The Path towards Humanized 3D Stem Cell-Based Models
by Mariana A. Branco, Tiago C. Nunes, Joaquim M. S. Cabral and Maria Margarida Diogo
Int. J. Mol. Sci. 2023, 24(5), 4857; https://doi.org/10.3390/ijms24054857 - 02 Mar 2023
Cited by 2 | Viewed by 1780
Abstract
Today, it is recognized that medicines will eventually be needed during pregnancy to help prevent to, ameliorate or treat an illness, either due to gestation-related medical conditions or pre-existing diseases. Adding to that, the rate of drug prescription to pregnant women has increased [...] Read more.
Today, it is recognized that medicines will eventually be needed during pregnancy to help prevent to, ameliorate or treat an illness, either due to gestation-related medical conditions or pre-existing diseases. Adding to that, the rate of drug prescription to pregnant women has increased over the past few years, in accordance with the increasing trend to postpone childbirth to a later age. However, in spite of these trends, information regarding teratogenic risk in humans is often missing for most of the purchased drugs. So far, animal models have been the gold standard to obtain teratogenic data, but inter-species differences have limited the suitability of those models to predict human-specific outcomes, contributing to misidentified human teratogenicity. Therefore, the development of physiologically relevant in vitro humanized models can be the key to surpassing this limitation. In this context, this review describes the pathway towards the introduction of human pluripotent stem cell-derived models in developmental toxicity studies. Moreover, as an illustration of their relevance, a particular emphasis will be placed on those models that recapitulate two very important early developmental stages, namely gastrulation and cardiac specification. Full article
(This article belongs to the Special Issue Organoids: The New 3D-Frontier to Model Different Diseases In Vitro)
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