Lung organoids provide animal alternative for nanomaterial testing

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Lung organoids grown by University of Manchester scientists have been shown to mimic the response of animals when exposed to certain nanomaterials.

The study at the University’s NanoCell Biology Lab at the Centre for Nanotechnology in Medicine is published in the journal Nano Today.

Though not expected to replace animal models completely, human organoids could soon lead to significant reductions in research animal numbers, the team led by cell biologist and nanotoxicologist Dr Sandra Vranic argues.

Grown in a dish from human stem cells, lung organoids are multicellular, three-dimensional structures that aim to recreate key features of human tissues such as cellular complexity and architecture.

To expose the organoid model to carbon-based nanomaterials, Dr Rahaf Issa, lead scientist in Dr Vranic’s group, developed a method to accurately dose and microinject nanomaterials into the organoid’s lumen.

It simulated the real-life exposure of the apical pulmonary epithelium, the outermost layer of cells lining respiratory passages within the lungs.

2D cell culture models ‘simplistic’

Existing animal research data has shown that a type of long and rigid multi-walled carbon nanotubes (MWCNT) can cause adverse effects in lungs, leading to persistent inflammation and fibrosis – a serious type of irreversible scarring in the lung.

Using the same biological endpoints, the team’s human lung organoids showed a similar biological response.

Graphene oxide (GO), 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 induced a more persistent interaction with the alveolar cells, with more limited mucin secretion and leading to the growth of fibrous tissue.

In a further development, the team are now developing and studying a human lung organoid that also contains an integrated immune cell component.

Professor Kostas Kostarelos, Chair of Nanomedicine at the University, said: “Current ‘2D testing’ of nanomaterials using two-dimensional cell culture models provide some understanding of cellular effects, but they are so simplistic as it can only partially depict the complex way cells communicate with each other. It certainly does not represent the complexity of the human pulmonary epithelium and may misrepresent the toxic potential of nanomaterials, for better or for worse.

“Though animals will still be needed in research for the foreseeable future, ‘3D’ organoids nevertheless are an exciting prospect in our research field and in research more generally as a human equivalent and animal alternative.”

Diana Spencer, Senior Digital Content Editor, DDW

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