Mini organs set for maximum success as new models can be used to individualise cancer therapy.
Organoids are three-dimensional bundles of cells grown in culture in a lab. Derived from stem cells, the organoid cells possess an incredible ability to organise themselves into tissue structures, meaning researchers have been able grow a whole range of tissues and mini-organs, including kidney, pancreas, liver, prostate and even brain tissue.
Longevity.Technology: This ability to grow so many different types of mini-organ in the lab has led to organoids becoming one of the most rapidly growing fields of biomedical research over the last few years. Not only does it mean specific tumours can be grown for screening and research, but that researchers can have access to tissues that haven’t been obtained invasively and are far better-suited to the job than animal samples.
The TRL score for this Longevity.Technology domain is currently set at: “Early proof of concept demonstrated in the laboratory”
The TRL score for the technology addressed in this article is: “Early proof of concept demonstrated in the laboratory”.
Back in 2008, a research team led by Professor Hans Clevers at the Hubrecht Institute at Utrecht University in the Netherlands, was trying to grow stem cells obtained from an adult intestine [1].
The team expected the cells to simply replicate themselves in the dish, but instead they self-organised, forming a replica gut in miniature with the associated villi and crypts present and functioning.
It was so unexpected that the Hubrecht team had a hard time trying to get their research published. However, once it had been, it became the blueprint for organoids created from stem cells obtained from epithelial cells, with research moving at a fast pace that shows no sign of slowing, especially in Japan, where research has benefitted from a wave of deregulation when it comes to stem cell science.
Organoids have allowed researchers and clinicians to make more precise diagnoses, as well as developing individual treatments based on a patient’s specific cancer. Rather than a best-fit model, the therapy can be specialised, incredibly useful given that no two cancers are molecularly alike. Organoids are also the ideal platform for assessing therapies in clinical trials.
Perhaps the largest leap in research using organoids, has been the development of ‘mini-brains’. Harder to develop because they are not based on epithelial cells, they were developed from neurons derived from embryonic stem cells and induced pluripotent stem cells by Madeline Lancaster, a researcher in Jürgen Knoblich’s lab at the Institute of Molecular Biotechnology in Vienna [2].
The brain is the most complicated and least understood organ in the body. Modelling it for research means either using animal brains (a considerable number of discoveries have failed to translate from animal model to human) or human brain cells (invasive and working with small samples reduces accuracy). Work done by Harvard Stem Cell Institute (HSCI)’s Paola Arlotta and her team have created pea-sized brain organoids that contain all the different types of brain cell [3].
And it’s not just in the lab where things are moving quickly; commercialising the technology is making the most of the opportunities in this sector. Professor Knoblich and Ms Lancaster have co-founded a spinout company called a:head to capitalise on their brain organoid success and Professor Clevers is also taking his lab’s technology to market.
“We set up a nonprofit foundation called Hubrecht Organoid Technology [Hub], which holds my lab’s patents — more than 20 so far,” he says. “In addition to carrying out research, Hub offers licences for drug screening and access to organoids in its biobanks for pre-clinical drug discovery and validation.” Hub is collaborating with Cellesce in Cardiff to scale up the production of organoids for research [4].
Researchers should remain mindful that growing organoids will need to be vascularised; as Michael Hufford, CEO of LyGenesis, a competitor in this space, told Longevity.Technology: “That’s the biggest challenge that the bio-printing and extracellular matrix folks have. How do you vascularise those tissues?”
3D bio-printing may offer glimpse of 2 sectors coming together to address vasculature and ultimately neural integration, as Dr Deepak Kalaskar, Associate Professor of Bioengineering at UCL recently told us. “Vascularisation is one of the challenges to be realised in 3D bioprinted tissue. I would say, we have made great progress in developing strategies based on innovative materials and printing technology to create networks similar to vascular structures. However, it’s very early work, we are at TRL 2-3 stage.”
Dr Kalaskar added. “The microenvironment for nerve tissue is very complex. So far our understanding of nerve tissue is limited to 2D culture. Most of work in this area focuses on disease model development to understand the pathology of various diseases such as brain cancer and neurodegenerative diseases. With bioprinting we are now able to study nerve tissue in a 3D environment. Similar to vasculature, we are making progress in our understanding of the 3D microenvironment to develop strategies to replicate this.”
LyGenesis recently raised $4m ahead of Phase 2a trials which we’re guessing is a bridge to a larger investment round in 2020. Judging by the pace of innovation in organoids we expect there will others seeking big rounds next year.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889692/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002496/
[3] https://hsci.harvard.edu/news/improved-human-brain-organoids-boost-neurological-disease-research
[4] https://www.ft.com/content/7557c884-9754-11e9-98b9-e38c177b152f
