An organoid that mimics the human intestine. Source: Yale Rosen, Flickr Commons
New methods published by the Broad Institute promise to revolutionize the scientific study of organs by offering a new model system to researchers: organoids. Organoids are miniature scale organs that function similarly to their larger cousins and are made via culturing differentiated stem cells. Organoids are a hot topic within biomedical research because they promise to allow more intensive macro-scale research into organ functionality and its relationship with genetics.With this transformational new model comes new informatics and polydisciplinary collaboration requirements that current researchers are not equipped to meet.
Organoids still can’t approximate the interactions that organs have with each other, but for basic research into pathology, they’re more than sufficient.1 2 Future researchers will use organoids as their primary cell culture format, displacing the decades-long reign of the cells-in-liquid-media culture methodology. Organoids will also displace animal models for some purposes, but not all. Researchers may finally be able to avoid hours of mouse organ dissection and tedious tissue sectioning, something that may be rendered even more streamlined with the use of innovative lab software.
Shaping the organoids
Making an organoid is more complex than setting up a regular cell culture, but not prohibitively so. To generate an organoid, researchers harvest stem cells, then drive them to differentiate via a chemical cocktail in the cell media. During the differentiation process, the cells are concentrated together, and their media is swapped to a specialized matrix media which encourages the cells to self-organize into organoids and provides them with a gelatinous scaffolding that they can use to aid their formation of a 3D structure.
As the cells grow in a dense clump and complete their differentiation, they migrate and divide to create a micro-scale organ of their cell type. Organs like livers and intestines are of special interest to model as they don’t have as many different types of cells as other organs do, and their internal structures are relatively well understood.3 Researchers are optimistic that organoids are workable models for most organs, provided that you’re willing to put in a little extra work. Much of this extra work involves experiment planning, data tracking and analysis, as generating organoids requires a lot of moving parts to come together seamlessly.
In particular, preparing an organoid requires at least the following elements:
- Pilot study data from liquid cell culture demonstrating the organoid study’s proof of concept
- Organoid study data indicating the methodology for organoid sourcing, assembly and downstream application
- Pluripotent stem cell harvesting methodology and metadata
- Pluripotent stem cell storage and culture maintenance records from before organoid experiment begins
- Organoid differentiation and induction media preparation records and supply chain data
- Generation and storage records of any experiment-specific biologics like viruses or antibodies
- Personnel scheduling for time-sensitive organoid development or analysis operations, of which there are likely many
Experimentation in 3D
In short, generating organoids will be a nightmare for labs that don’t have their experiment planning, scheduling, data tracking, inventory management and execution methodologies perfectly in harmony. Many will astutely point out that this means that generating organoids will be a nightmare for most labs. The organoid production process isn’t even the whole story, though.
After organoids are designed and grown, the real experimentation begins. Much like other novel models, experiments with organoids produce far more experimental data because researchers are still demonstrating comparability between the organoids that they generate and the traditional models.4 Adding the comparability testing requirement to other experimental needs demands examining many previously untouched variables to see if they’re relevant or not.
Organoids require an intense software package to organize the data that they’re capable of generating. Each individual organoid has several different levels of organization that each require analysis:
- Pluripotent stem cell characteristics before organoid formation
- Initial differentiated cell characteristics during each stage of differentiation
- Migrating cell characteristics; migration metadata
- Organoid surface cell characteristics
- Interior organoid cell characteristics
- Self-assembly of organoid macro structure
- Self-assembly of organoid microstructures
- Relationship between different areas of the organoid and each other
- Relationship between the organoid and its suspension
- Relationship between the organoid and any other parts of the experimental system such as other organoids or pathogens
- Transcriptome of organoid cells at each stage of development and at each level of organization
- Genetic and epigenetic factors which influence all the above
- Influence of all of the above on the epigenetics of organoid cells
With all of these factors in mind, it’s clear that each organoid experiment will be breaking into completely unknown territory in a wide variety of disciplines. Experimentation with organoids will generate data that will go beyond the scope of a single lab’s personnel quite easily. There’s simply no way that a single lab could have all of the skilled technicians, physiologists, cell biologists, molecular biologists, anatomists, pathologists and other specialists that creating and understanding organoid data requires.
The organoid model will require an extensive amount of collaboration with other people and groups in order to make sense out of the data and develop sensible experimental protocols—and besides, it’s likely that many different scientists will be interested in getting involved in organoid research once they hear about it. For these reasons, the information technology systems that most laboratories use will be insufficient for organoid research. Thankfully, there is a technology platform which can rise to the occasion of adding a third dimension to cell culture.
Collaborative Science is the experiment planning, data sharing and collaboration tool that will let your lab manage moving into 3D cell culturing with organoids. Using Collaborative Science, you’ll be able to ensure that all of your lab is on the same page and that all of your collaborators are kept up to date on your latest organoid production and experimental data. Contact us today to find out how you can use Collaborative Science to add the third dimension to your model systems and get the most out of organoid research.
- “Modelling kidney disease with CRISPR-mutant kidney organoids derived from pluripotent epiblast spheroids.” October 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620584/ ↩
- “Organoid Models of Human and Mouse Ductal Pancreatic Cancer.” December 2014, http://www.cell.com/cell/abstract/S0092-8674(14)01592-X?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS009286741401592X%3Fshowall%3Dtrue ↩
- “Modeling mouse and human development using organoid cultures.” 2015, http://dev.biologists.org/content/142/18/3113 ↩
- “Optimal experiment selection for parameter estimation in biological differential equation models.” 2012, http://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-13-181 ↩