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Organoids, Volume 3, Issue 4 (December 2024) – 3 articles

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14 pages, 3205 KiB  
Article
Establishment and Validation of Patient-Derived Non-Small Cell Lung Cancer Organoids as In Vitro Lung Cancer Models
by Raphael S. Werner, Jae-Hwi Jang, Markus Rechsteiner, Michaela B. Kirschner and Isabelle Opitz
Organoids 2024, 3(4), 281-294; https://doi.org/10.3390/organoids3040017 (registering DOI) - 9 Nov 2024
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Abstract
Background: Recent advances in the personalized treatment of non-small cell lung cancer (NSCLC) require representative in vitro model systems that reflect tumor heterogeneity and maintain the characteristic genetic aberrations. We therefore aimed to establish patient-derived NSCLC organoids that offer a reliable platform for [...] Read more.
Background: Recent advances in the personalized treatment of non-small cell lung cancer (NSCLC) require representative in vitro model systems that reflect tumor heterogeneity and maintain the characteristic genetic aberrations. We therefore aimed to establish patient-derived NSCLC organoids that offer a reliable platform for further investigations. Methods: NSCLC organoids were cultured between May 2020 and February 2022 from surgically resected NSCLC tissue specimens. After histological and immunohistochemical validation, genetic validation was performed by targeted next-generation sequencing of tissue and organoid specimens using the Oncomine Focus Assay (ThermoFisher Scientific). Results: From 37 resected NSCLC samples, 18 primary organoid cultures were successfully established and expanded during early passages. Upon histomorphological validation, organoids showed complementary characteristics when compared to the resected parental tumor, including adenocarcinoma, squamous cell carcinoma, mucoepidermoid carcinoma, and lung carcinoid differentiation. Among nine parental tumors, traceable genetic alterations were detected, and three corresponding organoids lines retained this mutational profile, including a KRAS p.Gly12Val mutation, KRAS p.Gly12Cys mutation, and RET-fusion. Conclusions: The establishment of primary NSCLC organoids from surgically resected tissue is feasible. Histological, immunohistochemical, and genetic validation is essential to identify representative NSCLC organoids that maintain the characteristics of the parental tumor. Overall, low establishment rates remain a challenge for broad clinical applications. Full article
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15 pages, 1134 KiB  
Review
Precision Medicine for Gastric Cancer: Current State of Organoid Drug Testing
by Tharindie N. Silva, Josephine A. Wright, Daniel L. Worthley and Susan L. Woods
Organoids 2024, 3(4), 266-280; https://doi.org/10.3390/organoids3040016 - 31 Oct 2024
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Abstract
Gastric cancer (GC) presents a significant health challenge and ranks as the fifth most common cancer in the world. Unfortunately, most patients with GC exhaust standard care treatment options due to late diagnosis and tumour heterogeneity that leads to drug resistance, resulting in [...] Read more.
Gastric cancer (GC) presents a significant health challenge and ranks as the fifth most common cancer in the world. Unfortunately, most patients with GC exhaust standard care treatment options due to late diagnosis and tumour heterogeneity that leads to drug resistance, resulting in poor survival outcomes. Potentially, this situation can be improved by personalising treatment choice. Organoids are an emerging cell model system that recapitulates tumour heterogeneity and drug responses. Coupled with genomic analysis, organoid culture can be used to guide personalised medicine. The GC organoid field, however, lacks standardised methodologies for assessing organoid drug sensitivities. Comparing results across different GC organoid studies and correlating organoid drug responses with patient outcomes is challenging. Hence, we aim to summarise the methodologies used in GC organoid drug testing and correlation with clinical outcomes and discuss design considerations and limitations to enhance the robustness of such studies in the future. Full article
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19 pages, 1247 KiB  
Review
Bioengineering Tooth and Periodontal Organoids from Stem and Progenitor Cells
by Fuad Gandhi Torizal, Syarifah Tiara Noorintan and Zakiya Gania
Organoids 2024, 3(4), 247-265; https://doi.org/10.3390/organoids3040015 - 3 Oct 2024
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Abstract
Tooth and periodontal organoids from stem and progenitor cells represent a significant advancement in regenerative dentistry, offering solutions for tooth loss and periodontal diseases. These organoids, which mimic the architecture and function of real organs, provide a cutting-edge platform for studying dental biology [...] Read more.
Tooth and periodontal organoids from stem and progenitor cells represent a significant advancement in regenerative dentistry, offering solutions for tooth loss and periodontal diseases. These organoids, which mimic the architecture and function of real organs, provide a cutting-edge platform for studying dental biology and developing therapies. Recent methodologies have been developed to optimize conditions for organoid production, advancing dental regenerative medicine, disease modeling, and developmental studies. The integration of bioengineering strategies with culture techniques enhances both our understanding and the therapeutic potential of these organoids. Additionally, factors such as the extracellular matrix, growth factors, and culture systems profoundly influence organoid formation and maturation. This review explores various bioengineering approaches for generating organoids, emphasizing the pivotal role of stem and progenitor cells. Full article
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