An Introduction to Organoids

Estimated Reading Time: 5 minutes

TL;DR

Building on last week’s post about iPSC cells, we discuss the emerging science of organoids, clusters of cells which capture some of the behavior of organs. Organoids can be grown from iPSC cells or from embryonic stem cells and provide powerful models of human biology and disease. 

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Organoids Recapitulate Complex Human Biology

Organoids are three dimensional clusters of cells that recapitulate some of the function of an organ. While cell cultures have been grown in the lab for decades, such cultures often fail to capture the microscopic biological and chemical environment of the organ (the “microenvironment.”) Organoids more closely match the true organ state and hold out the promise of allowing for systematic laboratory studies of organ (and tumor) behavior.

Intestinal organoid grown from Lgr5+ stem cells. Image and quote from source.

Methods for growing organoids can be surprisingly simple in some cases, with iPSC or stem cells embedded into a nutrient gel naturally growing into three dimensional organoids. Alternatively, growth factors can be provided that guide the development of the organoid as shown in the figure below.

Instructive growth factors regulating fate decisions in embryonic neural crest stem cells. Caption and image from (source).

In some cases, growth procedures can be yet more complicated, with brain organoids requiring months of preparation as the image below shows. Despite these complexities, the science of organoids has advanced so dramatically that bioethicists have raised concerns about experiments performed on brain organoids.

This flow chart outlines the basic steps to create a cerebral organoid. The process takes a span of months and the size of the organoid is limited to the availability of nutrients. Image and quote from source.

Improved Disease Models?

Drug discovery scientists hold out hope that organoids could usher in dramatic advances in medicine discovery. The construction of high fidelity organoids may permit nuanced models of human disease, allowing potential drugs to be tested in conditions closely matching patient bodies. Recent advances could allow for patient derived organoids that grow organoids directly from patient cells allowing for even more realistic models of patient disease as the image below shows. However, these technologies are still in early stages of deployment. Growing an organoid (and especially a patient derived organoid) remains a complex activity, and considerable infrastructure will have to mature before such techniques become mainstream. Newly emerging organoid-on-a-chip technology may help close the gap given time.

Schematic representation of four models for tumor cell culture in vitro. 2D cell line: after obtaining cells from ATCC, they can be grown in a 10 cm dish, and then visualized using light microscopy. 3D cell line: after obtaining cells from ATCC, they can be grown in a low attachment 96 well plate. 2D primary cells: after obtaining primary cells from a bladder cancer tumor, the cells can be grown in a 10 cm dish. However, after several passages, they lose their heterogeneity. Organoids: after obtaining primary cells from a bladder cancer tumor, the cells can be plated as organoids in 60 µL Matrigel droplets. Image and caption from source.

Weekly News Roundup

• https://www.quantamagazine.org/researchers-build-ai-that-builds-ai-20220125/: Hypernetworks could hold the promise to dramatically accelerate training of AI models, but considerable work will need to be done to prove these new ideas out.

• https://www.nature.com/articles/s41586-021-04223-6: Analog deep networks can potentially be trained with backpropagation in a new hybrid approach.

Feedback and Comments

Please feel free to email me directly (bharath@deepforestsci.com) with your feedback and comments! 

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Deep Into the Forest is a newsletter by Deep Forest Sciences, Inc. We’re a deep tech R&D company building an AI-powered scientific discovery engine. Partner with us to apply our foundational AI technologies to hard real-world problems. Get in touch with us at partnerships@deepforestsci.com! 

Credits

Author: Bharath Ramsundar, Ph.D.

Editor: Sandya Subramanian, Ph.D.