Organoids are mini organs on a minute scale, grown from stem cells in the lab for use in tests which would currently be performed on rodents. They involve minute quantities of chemicals – nanograms.
And now human mini-lungs grown by University of Manchester scientists, led by Dr Sandra Vranic, can mimic the response of animals when exposed to certain materials, thereby reducing research animal numbers.
Grown in a dish from human stem cells, lung organoids are multicellular, three-dimensional structures that aim to recreate key features of human tissues.
They are increasingly used to better understand pulmonary diseases, from cystic fibrosis to lung cancer, and infections like Covid.
However, their ability to show the effect of nanomaterials has so far not been possible. To expose the organoid model to nanomaterials, Dr Rahaf Issa, lead scientist in Dr Vranic’s group, developed a method to simulate the real-life exposure of cells lining our air passages within the lungs.
“With further validation, prolonged exposure, and the incorporation of an immune component, human lung organoids could greatly reduce the need for animals used in nanotoxicology research”, says Dr Vranic.
The human lung organoids showed a similar biological response, which validates them as tools for predicting responses in human lung tissue.
Graphene oxide, a flat, thin and flexible form of carbon nanomaterial, was found to be momentarily trapped out of harm’s way in a substance produced by the respiratory system called secretory mucin.
In contrast, MWCNT (another form of carbon) induced a more persistent interaction with the lung cells, with more limited mucin secretion that led to the growth of fibrous tissue.
In a further development, Drs Issa and Vranic, based at the university’s Centre for Nanotechnology in Medicine, are now developing and studying a groundbreaking human lung organoid that also contains an integrated immune cell component.
“Developed to encourage humane animal research, the 3Rs of replacement, reduction and refinement are now embedded in UK law and in many other countries,” says Dr Vranic.
“Public attitudes consistently show that support for animal research is conditional on the 3Rs being put into practice.”
Professor Kostas Kostarelos, Chair of Nanomedicine at the university said: “Although animals will still be needed in research for the foreseeable future, 3D organoids are nevertheless an exciting prospect in our research field and in research more generally as a human equivalent and animal alternative.
“Current 2D testing of nano-materials does not represent the complexity of the human pulmonary epithelium and may misrepresent the toxic potential of nanomaterials, for better or for worse.” But what a step forward.