Primary Lung Cancer Organoids for Personalized Medicine—Are They Ready for Clinical Use?

Despite many developments in recent years, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Therefore, additional research, aiming to further elucidate the underlying molecular mechanisms of malignant transformation and development of therapy resistance, as well as the identification of additional novel therapeutic avenues, is crucial. For this purpose, reliable in vitro models are indispensable, as they allow for quick identification of suspected oncogenic drivers or evaluation of novel therapeutic strategies in a timely and cost-effective fashion. However, standard two-dimensional cell culture systems, the most frequently used in vitro model, are usually not truly representative of the situation in a patient as these models lack the tumor heterogeneity, the surrounding tumor microenvironment and the three-dimensional complexity of a tumor in vitro. For this reason, 3D cell culture systems, in particular organoids generated from normal non-malignant cells or tumor cell-based organoids (tumoroids), have in recent years gained much attention as alternative in vitro model systems that more closely resemble the actual primary tumor. In this review, we provide an overview of the available literature in the field of NSCLC organoids, which might still be in its infancy, but is gaining momentum.

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Alzheimer’s Disease: Current Perspectives and Advances in Physiological Modeling

Bioengineering ◽

10.3390/bioengineering8120211 ◽

2021 ◽

Vol 8 (12) ◽

pp. 211

Author(s):

E. Josephine Boder ◽

Ipsita A. Banerjee

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cell Culture ◽

Stem Cell Differentiation ◽

Experimental Manipulation ◽

Model Systems ◽

Culture Systems ◽

Cell Culture Systems

Though Alzheimer’s disease (AD) is the most common cause of dementia, complete disease-modifying treatments are yet to be fully attained. Until recently, transgenic mice constituted most in vitro model systems of AD used for preclinical drug screening; however, these models have so far failed to adequately replicate the disease’s pathophysiology. However, the generation of humanized APOE4 mouse models has led to key discoveries. Recent advances in stem cell differentiation techniques and the development of induced pluripotent stem cells (iPSCs) have facilitated the development of novel in vitro devices. These “microphysiological” systems—in vitro human cell culture systems designed to replicate in vivo physiology—employ varying levels of biomimicry and engineering control. Spheroid-based organoids, 3D cell culture systems, and microfluidic devices or a combination of these have the potential to replicate AD pathophysiology and pathogenesis in vitro and thus serve as both tools for testing therapeutics and models for experimental manipulation.

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[4] Avian hematopoietic cell culture: In vitro model systems to study oncogenic transformation of hematopoietic cells

Oncogene techniques - Methods in Enzymology ◽

10.1016/0076-6879(95)54006-7 ◽

1995 ◽

pp. 41-76 ◽

Cited By ~ 19

Author(s):

Hartmut Beug ◽

Peter Steinlein ◽

Petr Bartunek ◽

Michael J. Hayman

Keyword(s):

Cell Culture ◽

In Vitro Model ◽

Hematopoietic Cells ◽

Hematopoietic Cell ◽

Model Systems ◽

Oncogenic Transformation ◽

Culture In Vitro ◽

Vitro Model

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Human 3-dimensional liver organoids: in vitro model systems to study liver diseases

10.1055/s-0039-3402185 ◽

2020 ◽

Author(s):

H Gaitantzi ◽

C Cai ◽

S Asawa ◽

K Böttcher ◽

M Ebert ◽

...

Keyword(s):

Liver Diseases ◽

In Vitro Model ◽

Model Systems ◽

3 Dimensional ◽

Vitro Model ◽

Liver Organoids

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Recent Progress in Prediction Systems for Drug-induced Liver Injury Using in vitro Cell Culture

Drug Metabolism Letters ◽

10.2174/1872312814666201202112610 ◽

2020 ◽

Vol 14 ◽

Author(s):

Shogo Ozawa ◽

Toshitaka Miura ◽

Jun Terashima ◽

Wataru Habano ◽

Seiichi Ishida

Keyword(s):

Cell Culture ◽

Recent Progress ◽

Inflammatory Cells ◽

Protein Adducts ◽

In Vitro Assays ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Culture Systems ◽

Cell Culture Systems

Background: In order to avoid drug-induced liver injury (DILI), in vitro assays, which enable the assessment of both metabolic activation and immune reaction processes that ultimately result in DILI, are needed. Objective: In this study, the recent progress in the application of in vitro assays using cell culture systems is reviewed for potential DILI-causing drugs/xenobiotics and a mechanistic study on DILI, as well as for the limitations of in vitro cell culture systems for DILI research. Methods: Information related to DILI was collected through a literature search of the PubMed database. Results: The initial biological event for the onset of DILI is the formation of cellular protein adducts after drugs have been metabolically activated by drug metabolizing enzymes. The damaged peptides derived from protein adducts lead to the activation of CD4+ helper T lymphocytes and recognition by CD8+ cytotoxic T lymphocytes, which destroy hepatocytes through immunological reactions. Because DILI is a major cause of drug attrition and drug withdrawal, numerous in vitro systems consisting of hepatocytes and immune/inflammatory cells, or spheroids of human primary hepatocytes containing non-parenchymal cells have been developed. These cellular-based systems have identified DILIinducing drugs with approximately 50% sensitivity and 90% specificity. Conclusion: Different co-culture systems consisting of human hepatocyte-derived cells and other immune/inflammatory cells have enabled the identification of DILI-causing drugs and of the actual mechanisms of action.

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In Vitro Model Systems for Exploring Oral Biofilms: From Single‐Species Populations to Complex Multi‐Species Communities

Journal of Applied Microbiology ◽

10.1111/jam.15200 ◽

2021 ◽

Author(s):

Ting L. Luo ◽

Michael E. Vanek ◽

Carlos Gonzalez‐Cabezas ◽

Carl F. Marrs ◽

Betsy Foxman ◽

...

Keyword(s):

In Vitro Model ◽

Single Species ◽

Model Systems ◽

Oral Biofilms ◽

Vitro Model

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Mammary gland 3D cell culture systems in farm animals

Veterinary Research ◽

10.1186/s13567-021-00947-5 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Laurence Finot ◽

Eric Chanat ◽

Frederic Dessauge

Keyword(s):

Cell Culture ◽

Mammary Gland ◽

Bacterial Infections ◽

Three Dimensional ◽

3D Cell Culture ◽

Farm Animals ◽

Culture Systems ◽

Cell Culture Systems

AbstractIn vivo study of tissue or organ biology in mammals is very complex and progress is slowed by poor accessibility of samples and ethical concerns. Fortunately, however, advances in stem cell identification and culture have made it possible to derive in vitro 3D “tissues” called organoids, these three-dimensional structures partly or fully mimicking the in vivo functioning of organs. The mammary gland produces milk, the source of nutrition for newborn mammals. Milk is synthesized and secreted by the differentiated polarized mammary epithelial cells of the gland. Reconstructing in vitro a mammary-like structure mimicking the functional tissue represents a major challenge in mammary gland biology, especially for farm animals for which specific agronomic questions arise. This would greatly facilitate the study of mammary gland development, milk secretion processes and pathological effects of viral or bacterial infections at the cellular level, all with the objective of improving milk production at the animal level. With this aim, various 3D cell culture models have been developed such as mammospheres and, more recently, efforts to develop organoids in vitro have been considerable. Researchers are now starting to draw inspiration from other fields, such as bioengineering, to generate organoids that would be more physiologically relevant. In this chapter, we will discuss 3D cell culture systems as organoids and their relevance for agronomic research.

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Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms

Molecules ◽

10.3390/molecules26061676 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1676

Author(s):

Giulia Rossi ◽

Martina Placidi ◽

Chiara Castellini ◽

Francesco Rea ◽

Settimio D'Andrea ◽

...

Keyword(s):

In Vitro Model ◽

Molecular Mechanisms ◽

Biological Effects ◽

Cellular Damage ◽

X Rays ◽

Adolescent Cancer ◽

Radiation Induced ◽

Vitro Model ◽

Underlying Mechanisms

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

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