Summary

An organoid is a 3D multicellular in vitro tissue construct that mimics its corresponding in vivo organ, such that it can be used to study aspects of that organ in the tissue culture dish. Although 3D tissue culture is decades old, the word organoid is today most commonly used to describe such constructs derived from stem cells; these could be either pluripotent (embryonic or induced) or adult stem cells (ACS) from various organs. Organoids hold tremendous promise as a tool for more safe and personalised drug development. It is closely related to Bioprinting which is a process by which organoids are created. **Cindy: also closely related with organ-on-a-chip

Viability (3)

The technique for growing organoids has rapidly improved since the early 2010s. The technology is already yielding small-scale results with research groups using organoids to study a variety of diseases including the zika virus and other infectious diseases, cystic fibrosis and cancers. Despite progress there are still many challenges to overcome before organoids can reach broad utility, including a lack of high-fidelity cell types, limited maturation, atypical physiology, and lack of arealization.

Drivers (5)

On the supply-side, organoids were made practical with the introduction of induced pluripotent stem cells (iPSC) technology from 2007. Before iPSC, human stem cells from human embryos at the blastocyst stage were needed as a source of usable human cells, which raises ethical concerns as well as being in short supply. iPSC provided an almost limitless supply of human stem cells as well as the ability to generate patient-specific stem cells. On the demand-side, organoids provide for the first time the ability to observe and test human characteristics and disease in human cells rather than in mice or other animals. After 30 years of animal model systems, the limitations of such models in emulating human pathophysiology are clear, especially for uniquely human diseases such as neuropsychiatric or neurodevelopmental diseases. Organoids offer the potential for a scalable pipeline of biobanking and in vitro disease modelling for personalised medicine dramatically improving the speed, efficacy and safety of drug development.

Novelty (4)

Organoids compete with other model systems for human biology and medicine. The most common model organisms that are used in biomedical research are roundworm (Caenorhabditis elegans), fruit fly (Drosophila melanogaster), zebrafish (Danio rerio) and house mouse (Mus musculus), along with patient-derived cell lines, and patient-derived xenografts (PDX). Human organoids are competitive across all dimensions including ease of establishing system, ease of maintenance, recapitulation of developmental biology, duration of experiments, genetic manipulation, genome-wide screening, and physiological complexity. Where organoids shine is in the recapitulation of human physiology against which only xenografts and cell lines offer similar benefit, but without the richness of information yielded by organoids.

Diffusion (2)

Organoids still lack vasculature and immune cells and other cellular components and so are not currently viable for transplantation and accurate disease modelling. The expectation is organoids will get increasingly complex by connecting organoids together, but research here still has some way to go. Adoption will be particularly challenging because of the ethical questions raised particularly by cerebral organoids. The development of celebral organoids lets researchers explore consciousness but as of yet science does not have a theory of consciousness and as such we lack a suitable ethical framework.

Impact (5) High certainty

Forecast to be a $12 billion market in 2030 predominately on the back of tumour modelling and biobanking. This forecast assumes limited further progress in organoid research. Assuming the development of complex organoids with vasculation and immune cells, the impact of organoids will be 10x predictions. The convergence with Genomics and Optogenetics should allow cell-specific modulation making organoids much more effective for drug development than animal testing delivering on the promise of personalised medicine. More speculatively, celebral organoids can play an important role in neuroscience as a cheaper tool for research which could lead to a theory of consciousness and contribute meaningfully to the development of more general and efficient artificial intelligence.

Timing (2025-2030) Medium certainty

A $1.7 billion dollar market today with growth rate dependant on how quickly organoids can become more complex and networked as assembloids. The technical hurdles point at a 2030+ timeline especially because of the vasculation complexity and the complex interaction with immune cells. But the FDA Modernization Act 2.0 which passed in the United State Senate in September replaces the term “animal” with “nonclinical test” defined as in vitro, in silico, in chemico, and other nonhuman in vivo testing that may include animal tests. This bill will be a major catalyst for organoid development and with regulatory tailwinds, with medium certainly we can expect market impact in the 2025-2030 timeframe.