scholarly journals Patient-Derived Cancer Organoids for Precision Oncology Treatment

2021 ◽  
Author(s):  
Mark Pernik ◽  
Cylaina Bird ◽  
Jeffrey Traylor ◽  
Diana Shi ◽  
Timothy Richardson ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Three Dimensional ◽  
Clinical Applications ◽  
Cellular Heterogeneity ◽  
Precision Oncology ◽  
History Of ◽  
Oncology Treatment ◽  
Parental Tumor ◽  
In Vitro Cell Lines

The emergence of three-dimensional human organoids has opened the door for development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. Mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource- and time-intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell-cell and cell-stromal interactions, tumor microenvironment, and therapeutic responsiveness. PDO models and drug screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant timeframes and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.

scholarly journals Patient-Derived Cancer Organoids for Precision Oncology Treatment

2021 ◽  
Vol 11 (5) ◽  
pp. 423
Author(s):  
Mark N. Pernik ◽  
Cylaina E. Bird ◽  
Jeffrey I. Traylor ◽  
Diana D. Shi ◽  
Timothy E. Richardson ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Three Dimensional ◽  
Cellular Heterogeneity ◽  
Precision Oncology ◽  
History Of ◽  
Oncology Treatment ◽  
Parental Tumor ◽  
In Vitro Cell Lines ◽  
Time Frames

The emergence of three-dimensional human organoids has opened the door for the development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. The mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource and time intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell–cell and cell–stroma interactions, the tumor microenvironment, and therapeutic responsiveness. PDO models and drug-screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant time frames and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.

scholarly journals A brief history of organoids

2020 ◽  
Vol 319 (1) ◽  
pp. C151-C165 ◽  
Author(s):  
Claudia Corrò ◽  
Laura Novellasdemunt ◽  
Vivian S.W. Li
Keyword(s):  
Cell Cultures ◽  
Three Dimensional ◽  
3D Models ◽  
Cellular Heterogeneity ◽  
Potential Applications ◽  
History Of ◽  
In Vitro Cell Cultures ◽  
Structure And Functions

In vitro cell cultures are crucial research tools for modeling human development and diseases. Although the conventional monolayer cell cultures have been widely used in the past, the lack of tissue architecture and complexity of such model fails to inform the true biological processes in vivo. Recent advances in the organoid technology have revolutionized the in vitro culture tools for biomedical research by creating powerful three-dimensional (3D) models to recapitulate the cellular heterogeneity, structure, and functions of the primary tissues. Such organoid technology enables researchers to recreate human organs and diseases in a dish and thus holds great promises for many translational applications such as regenerative medicine, drug discovery, and precision medicine. In this review, we provide an overview of the organoid history and development. We discuss the strengths and limitations of organoids as well as their potential applications in the laboratory and the clinic.

scholarly journals Organoids of the female reproductive tract

2021 ◽  
Vol 99 (4) ◽  
pp. 531-553 ◽  
Author(s):  
Cindrilla Chumduri ◽  
Margherita Y. Turco
Keyword(s):  
Reproductive Tract ◽  
Personalised Medicine ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Experimental Models ◽  
Female Reproductive Tract ◽  
Cellular Heterogeneity ◽  
Dynamic Regulation ◽  
Pregnancy And Childbirth

AbstractHealthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.

scholarly journals Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 74 ◽  
Author(s):  
Takeshi Namekawa ◽  
Kazuhiro Ikeda ◽  
Kuniko Horie-Inoue ◽  
Satoshi Inoue
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Three Dimensional ◽  
Preclinical Study ◽  
Cellular Heterogeneity ◽  
Preclinical Model ◽  
Immunodeficient Mice ◽  
Metastatic Lesions ◽  
Pdx Models

Various preclinical models have been developed to clarify the pathophysiology of prostate cancer (PCa). Traditional PCa cell lines from clinical metastatic lesions, as exemplified by DU-145, PC-3, and LNCaP cells, are useful tools to define mechanisms underlying tumorigenesis and drug resistance. Cell line-based experiments, however, have limitations for preclinical studies because those cells are basically adapted to 2-dimensional monolayer culture conditions, in which the majority of primary PCa cells cannot survive. Recent tissue engineering enables generation of PCa patient-derived xenografts (PDXs) from both primary and metastatic lesions. Compared with fresh PCa tissue transplantation in athymic mice, co-injection of PCa tissues with extracellular matrix in highly immunodeficient mice has remarkably improved the success rate of PDX generation. PDX models have advantages to appropriately recapitulate the molecular diversity, cellular heterogeneity, and histology of original patient tumors. In contrast to PDX models, patient-derived organoid and spheroid PCa models in 3-dimensional culture are more feasible tools for in vitro studies for retaining the characteristics of patient tumors. In this article, we review PCa preclinical model cell lines and their sublines, PDXs, and patient-derived organoid and spheroid models. These PCa models will be applied to the development of new strategies for cancer precision medicine.

scholarly journals The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update

2021 ◽  
Vol 22 (14) ◽  
pp. 7667
Author(s):  
Joseph Azar ◽  
Hisham F. Bahmad ◽  
Darine Daher ◽  
Maya M. Moubarak ◽  
Ola Hadadeh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Modeling ◽  
New Technology ◽  
Three Dimensional ◽  
Cell Types ◽  
Clinical Applications ◽  
In Vitro Drug Screening

Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host–microbe interaction. The use of stem cells—that have self-renewal capacity to proliferate and differentiate into specialized cell types—for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications.

scholarly journals Bioreactor-Based Tumor Tissue Engineering

Acta Naturae ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 44-58 ◽  
Author(s):  
A. E. Guller ◽  
P. N. Grebenyuk ◽  
A. B. Shekhter ◽  
A. V. Zvyagin ◽  
S. M. Deyev
Keyword(s):  
Tissue Engineering ◽  
Cancer Biology ◽  
Tumor Tissue ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Laboratory Animals ◽  
Malignant Neoplasms ◽  
Successful Implementation ◽  
Engineering Technology

This review focuses on modeling of cancer tumors using tissue engineering technology. Tumor tissue engineering (TTE) is a new method of three-dimensional (3D) simulation of malignant neoplasms. Design and development of complex tissue engineering constructs (TECs) that include cancer cells, cell-bearing scaffolds acting as the extracellular matrix, and other components of the tumor microenvironment is at the core of this approach. Although TECs can be transplanted into laboratory animals, the specific aim of TTE is the most realistic reproduction and long-term maintenance of the simulated tumor properties in vitro for cancer biology research and for the development of new methods of diagnosis and treatment of malignant neoplasms. Successful implementation of this challenging idea depends on bioreactor technology, which will enable optimization of culture conditions and control of tumor TECs development. In this review, we analyze the most popular bioreactor types in TTE and the emerging applications.

scholarly journals Patient-Derived Organoids in Precision Medicine: Drug Screening, Organoid-on-a-Chip and Living Organoid Biobank

2021 ◽  
Vol 11 ◽  
Author(s):  
Zilong Zhou ◽  
Lele Cong ◽  
Xianling Cong
Keyword(s):  
Three Dimensional ◽  
Patient Specific ◽  
Medical Decisions ◽  
Future Directions ◽  
Self Assembling ◽  
Key Characteristics ◽  
Recent Developments ◽  
Cancer Types ◽  
Parental Tumor

Organoids are in vitro self-assembling, organ-like, three-dimensional cellular structures that stably retain key characteristics of the respective organs. Organoids can be generated from healthy or pathological tissues derived from patients. Cancer organoid culture platforms have several advantages, including conservation of the cellular composition that captures the heterogeneity and pharmacotypic signatures of the parental tumor. This platform has provided new opportunities to fill the gap between cancer research and clinical outcomes. Clinical trials have been performed using patient-derived organoids (PDO) as a tool for personalized medical decisions to predict patients’ responses to therapeutic regimens and potentially improve treatment outcomes. Living organoid biobanks encompassing several cancer types have been established, providing a representative collection of well-characterized models that will facilitate drug development. In this review, we highlight recent developments in the generation of organoid cultures and PDO biobanks, in preclinical drug discovery, and methods to design a functional organoid-on-a-chip combined with microfluidic. In addition, we discuss the advantages as well as limitations of human organoids in patient-specific therapy and highlight possible future directions.

scholarly journals Photodynamic Therapy-Mediated Immune Responses in Three-Dimensional Tumor Models

2021 ◽  
Vol 22 (23) ◽  
pp. 12618
Author(s):  
Nkune Williams Nkune ◽  
Nokuphila Winifred Nompumelelo Simelane ◽  
Hanieh Montaseri ◽  
Heidi Abrahamse
Keyword(s):  
Photodynamic Therapy ◽  
Immune Responses ◽  
Three Dimensional ◽  
Tumor Model ◽  
Experimental Models ◽  
Cellular Heterogeneity ◽  
Tumor Models ◽  
Cellular Environment

Photodynamic therapy (PDT) is a promising non-invasive phototherapeutic approach for cancer therapy that can eliminate local tumor cells and produce systemic antitumor immune responses. In recent years, significant efforts have been made in developing strategies to further investigate the immune mechanisms triggered by PDT. The majority of in vitro experimental models still rely on the two-dimensional (2D) cell cultures that do not mimic a three-dimensional (3D) cellular environment in the human body, such as cellular heterogeneity, nutrient gradient, growth mechanisms, and the interaction between cells as well as the extracellular matrix (ECM) and therapeutic resistance to anticancer treatments. In addition, in vivo animal studies are highly expensive and time consuming, which may also show physiological discrepancies between animals and humans. In this sense, there is growing interest in the utilization of 3D tumor models, since they precisely mimic different features of solid tumors. This review summarizes the characteristics and techniques for 3D tumor model generation. Furthermore, we provide an overview of innate and adaptive immune responses induced by PDT in several in vitro and in vivo tumor models. Future perspectives are highlighted for further enhancing PDT immune responses as well as ideal experimental models for antitumor immune response studies.

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