The year of the organoid

A brave new world of lab-grown body parts

Science and technology

The brain-in-a-jar is one of science fiction’s creepier ideas. It is a safe prediction that 2016 will not see such literally disembodied people become reality. What it will see, though, is the blossoming of a technology that lets scientists grow things resembling brains—and also livers, kidneys, intestines and many other body parts—in glass vessels in laboratories.

Over the course of 2016 these simulacra, known as organoids, will begin to enter routine medical use as ways of testing drugs. They will also, by illuminating the way real organs grow, cast light on diseases caused during embryonic development. Eventually, though probably not in 2016, some will even be made good enough to be transplanted into people, to replace diseased or failing natural organs.

Hans Clevers, of the Hubrecht Institute in the Netherlands, has grown “intestinoids” that will permit two novel sorts of drug testing. These will start being rolled out in earnest in 2016. One is for cystic fibrosis, a disease that gums up both the lungs and the intestines, eventually killing the patient. The other is for bowel cancer.

Organoids are grown from stem cells similar to those found in embryos, though they are actually obtained either from existing organs, or by treating skin cells with certain biochemicals to persuade them to turn into stem cells. Organoids thus created have the genetic characteristics of the people they are taken from, and so respond to drugs as would the corresponding organ of the person in question.

Cystic fibrosis is caused by a flaw in a particular gene. Different flaws in this gene, however, respond best to different treatments, and the details are not well understood. Dr Clevers plans to recruit all willing cystic-fibrosis patients in the Netherlands, grow intestinoids derived from their intestinal cells, and test the results against a range of drugs. That will identify the best treatment for each patient. Bowel cancer is even more complicated genetically, but the same principle applies. The organoid approach can create “tumouroids” as well. Hundreds of these, derived from a biopsy of an individual tumour, can be grown simultaneously and screened against every drug that could conceivably help, to see which actually do so.

Nor is Dr Clevers alone in this approach. Melissa Little of the Royal Children’s Hospital, in Melbourne, Australia, for example, is planning to use it to understand the treatment of polycystic renal disease (PRD). She is coaxing kidney stem cells into forming nephrons, the urine-generating units of the organ. These then create “kidneyoids” a few millimetres across. Dr Little suspects that about half of cases of PRD are underpinned by genetic problems, and she hopes, in the year ahead, to start screening drugs to find out which work best against what. At the Memorial Sloan Kettering Cancer Centre, in New York, Yu Chen is taking a similar approach to laboratory versions of prostate tumours.

Grow-it-yourself liver

In Yokohama, in Japan, meanwhile, Takanori Takebe and his colleagues are working on liver organoids. These, because of the liver’s protean ability to grow and regenerate rapidly, are likely to be the first organoids used for actual transplants, though not in 2016. The coming year will, however, see them deployed for the toxicity testing of drug candidates. This will be a particularly valuable use of the technology. One of the liver’s jobs is to break down potential poisons, which drugs are. But animal tests of drugs often give different answers from tests on people. Using organoids should stop the wasteful and potentially dangerous testing in human clinical trials of drugs that then prove too toxic to deploy.

Last, 2016 will see organoids put through their paces as tools that can help researchers understand how real organs develop, and what can go wrong with that process. Here, the brains-in-a-jar will come into their own, for there is a chance that studying them will crack open the mysteries of conditions such as schizophrenia and autism that seem to get “baked into” the organ early on, as neural connections develop within it.

This approach has already yielded one lead in the case of autism. Flora Vaccarino’s group at Yale have found a gene known to be important in neuron formation to be much more active in brainoids derived from people with a certain sort of autism than in their non-autistic confrères. Other genes are surely lurking, and may come to light in 2016. And Dr Vaccarino is not alone in her quest. Sergiu Pasca of Stanford University, is working on it too, particularly with regard to schizophrenia, and both he and Madeline Lancaster of Cambridge University, who created the first brainoids, are looking into the more existential question of whether the neural tissue in human brainoids differs from that in brainoids derived from other species in ways that might illuminate what makes Homo sapiens so special.

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