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MISpheroID – a knowledgebase and transparency tool for spheroid based research

Edinburgh researchers are part of international team developing improved standards and practices for three-dimensional (3D) cell culture models: November 2021

Image showing different types of cancer cells grown as spheroids in various cell culture media (for details see Peirsman et al.
Different types of cancer cells grown as spheroids in various cell culture media (for details see Peirsman et al. Nat Methods. 2021;18:1294-1303).

Human and animal cell culture techniques - growing human or animal cells under controlled conditions outside their natural environment - represent one of key technologies used in modern biomedical research. Their foundations had been established in late nineteenth century and they became a standard laboratory practice in the twentieth century. Over the years, cell culture techniques contributed to a broad spectrum of breakthrough discoveries including introduction of new vaccines and medicines. Importantly, these techniques are being continuously improved to model complex biological processes taking place in our bodies. While most experiments in the 20th century were 2D-based (in 2D cultures cells are grown on a flat surface, such as the bottom of a petri dish or flask), the end of twentieth century and early twenty‐first century brought the progress in 3D cell culture technology and created the possibility of the tissue engineering and the regenerative medicine development.

One of the 3D cell culture techniques used nowadays to provide better insights into cancer related processes such as cancer cell migration, invasion and drug resistance are so called spheroid cultures, cancer cells grown as near-spherical multicellular aggregates. Unfortunately, as it often happens with novel technologies, different laboratories frequently use different approaches and there is no consensus or evaluation of minimum information criteria appropriate for spheroid research. To address this problem and speed up further improvements in utility of spheroid cultures for biomedical research, scientists from several countries including Belgium, Hungary, Italy, Portugal, France, Austria, Finland, Germany, Canada, United States and United Kingdom, created a MISpheroID consortium. The consortium aims to provide new tools and better guidance for researchers interested in 3D cell culture techniques. It includes scientists from the Institute of Genetics and Cancer in Edinburgh.

In a recent paper published in the journal Nature Methods, MISpheroID investigators, including Prof Neil Carragher and Dr John Dawson from Cancer Research UK Edinburgh Centre, describe development of MISpheroID: a knowledgebase and transparency tool for minimum information in spheroid identity. The researchers performed analysis of experimental parameters in 3,058 published spheroid-related experiments. They also performed in-depth empirical evaluation and interlaboratory validation of selected variations in methodological setups. Their findings confirmed that there is significant diversity in spheroid generation protocols and highlighted a lack of transparency in reporting standards. The MISpheroID online resource establishes a thorough and searchable knowledgebase of spheroid experiments that will grow through continued engagement from the research community. The authors define improved standards for reporting (including MISpheroID string, a minimum set of experimental parameters required to report spheroid research) and invite the community to upload spheroid experiments into the database. Each uploaded annotated experiment receives a MISPheroID string and unique registration code.     

Edinburgh researchers are planning on using the MISpheroID tool as part of the ongoing CRUK funded research within the frame of accelerator award titled “Accelerating our ability to understand and target complexity and heterogeneity in cancer through automated imaging of 3D cancer models including patient-derived organoids”.

The use of 3-dimensional (3D) in vitro models to more faithfully recapitulate in vivo tumour biology within the laboratory is accelerating rapidly as a result of advances in 3D bioprinting, tissue organoids, microfluidic and automated high content confocal screening technologies. However, currently there are no established 3D assay standards or best practice, as a result different laboratories are using different methods and reagents to perform 3D experiments, including thousands of drug screening studies in tumour spheroid assays. The lack of assay standards and consistency in 3D tumour spheroid protocols has hampered inter-laboratory reproducibility and interpretation of results from the published literature. The MiSpheroID database shares experimental data and spheroid characteristics of >1,500 3D spheroid experiments and provides a recommended minimum information for spheroid culture. Researchers can consult this database and contribute by sharing experimental data of their own spheroid experiments, thereby increasing transparency in the spheroid research field

Professor Neil CarragherUniversity of Edinburgh

Related Links

Article in Nature Methods: https://www.nature.com/articles/s41592-021-01291-4

“Towards spheroid-omics” – commentary in Nature Methods: https://www.nature.com/articles/s41592-021-01311-3

MISpheroID online web resource: https://www.mispheroid.org/

Advancing microscopy to accelerate understanding of complexity and heterogeneity of 3D cancer –CRUK Accelerator project website: https://mach3cancer.org/

Professor Neil Carragher Group website: https://www.ed.ac.uk/cancer-centre/research/carragher-group

Interesting open access text about history of cell culture techniques: https://www.intechopen.com/chapters/53566

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