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Organoids Culture in Cancer

By: Samieh Asadian.Molecular Medicine Ph.D candidate.School of Medicine, QUMS.

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Organoid is a buzzword today. Everyone is talking about organoids in the mass media and biomedical literature. But what are organoids?

How can we define it? In simple terms organoid is miniature organ in vitro,

but scientifically, definition could be more complex.

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Introduction

Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation.

Recent advances in three-dimensional(3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues.

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History The first anatomical basis studies

organs represented combinations of a few fundamental tissues.

First definition of epithelium, connective tissue,nerve,muscle and blood as the universal tissues.

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https://Openbio.co.uk

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Biology of spheroids:CSCs grown as spheroids

www.mdpi.com

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Cancer cell linespatient-derived tumor xenograftsorganoids

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Https://Nature.com

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First provide an overview of the commonly used cellular inputs and culture formats.

Discuss how these experimental systems have been used.

Provide examples of how 3D culture techniques can be used to advance therapeutic approaches.

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Cellular inputs into 3D cultureWhole-organ and organ-slice cultures.

Tissue organoids.

Stem cell organoids.

Reaggregated single-cell suspensions.

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The major categories of cell culture.2.5D cultures.3D‑embedded cultures.Mechanically supported cultures.

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The role of the microenvironment in regulating epithelial function.

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Therapeutic applications of three-dimensional culture

Predictive assays

Prognostic assays

Preclinical therapeutic

testing

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Key Strengths and Weaknesses of 3D Models•Advantages• Cell morphology and signaling are often more physiological than routine 2D cell culture•Permit rapid experimental manipulations and testing of hypotheses• Permit much better real-time and/or fixed imaging by microscopy than in animalsDisadvantages• Vary in their ability to mimic in vivo tissue conditions • Currently lack vasculature and normal transport of small molecules, host immune responses, and other cell-cell interactions• Generally mimic static or short-term conditions, whereas in vivo systems often progress

DOI 10.1016/j.cell.2007.08.00

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Benign organoid culture

Dr. Hans Clevers

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Cancer organoid culturesProstate cancer organoids

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Human breast tumors are readily digested into tumor organoids to study the biology of tumor cell clusters in complex environments using patient tissues.

http://research.fhcrc.org/cheung/en/research.html

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A New Era of Personalized Medicine

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The landscape of translational oncology has shifted dramatically over the past 10 years, characterized by the introduction of ever-more-sophisticated molecular tools into the clinic

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Translational cancer-biology studies have markedly improved preclinical models applicable for therapeutics development, as well as our understanding of the roles of inflammation and altered intermediary metabolism in carcinogenesis.

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Translational cancer diagnostics and therapeutics have been revolutionized by the molecular characterization of human tumours, a process that now underlies the development of molecularly-targeted, rather than broadly cytotoxic, anticancer therapies

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Improvements in molecular tumour-classification techniques will permit their widespread application for patients at diagnosis, disease recurrence, and during therapy, supporting continuous adaptation of therapeutic approaches to evolving tumour characteristics

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Professor Hans Clevers, a senior author at the Hubrecht Institute

"Often, the jump from studying a cancer treatment in cells to performing a successful patient trial is too wide. Organoids are so experimentally tractable that they can answer many of our questions about cancers, bridging this gap. Not only can organoids save time and resources, we hope that they will one day let us see how treatments will work in an individual's unique cancer."

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An Exploding Field

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References Three-dimensional organotypic culture: experimental models of

mammalian biology and disease Eliah R. Shamir and Andrew J. Ewald.

Nature Reviews Molecular Cell Biology | AOP, published online 17

September 2014; doi:10.1038/nrm3873.

Modeling Tissue Morphogenesis and Cancer in 3D .Kenneth M. Yamada1, and Edna Cukierman. DOI 10.1016/j.cell.2007.08.006.

Organoid Development in Cancer Genome Discovery. Dong Gao1 and Yu Chen1, Curr Opin Genet Dev. 2015 February ; 30: 42–48.

doi:10.1016/j.gde.2015.02.007.

Organoids derived from digestive tract, liver, and pancreas. An Tao XU, Jin Lu TONG & Zhi Hua RAN. Journal of Digestive Diseases 2016; 17; 3–10.

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Organoid cultures for the analysis of cancer phenotypes. Norman Sachs and Hans Clevers. http://dx.doi.org/10.1016/j.gde.2013.11.012 .

Translational research in oncology—10 years of progress and future prospects. James H. Doroshow and Shivaani Kummar. Doroshow, J. H. & Kummar, S. Nat. Rev. Clin. Oncol. 11, 649–662 (2014); published online

7 October 2014.

Contribution of three-dimensional culture to cancer research. Critical Reviews in Oncology:Hematology 36 (2000) 59–60.

Concise Review: The Relevance of Human Stem Cell-Derived Organoid Models for Epithelial Translational Medicine. ROBERT E. HYNDS, ADAM GIANGRECO. Received October 1, 2012; accepted for publication November 15, 2012; first published online in STEM CELLS EXPRESS December 3, 2012.

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