How we’ll transplant tiny organ-like blobs of cells into people

To the naked eye, organoids aren't much to look at. They're basically tiny blobs. Closer inspection reveals their true complexity: these lab-grown balls of cells can resemble miniature organs. So far, organoids have mostly been used for research. But teams have started transplanting them into animals with the hope of curing disease. Humans are next-albeit some way off. Let's say in 10 years ... maybe.

The best known of these organoids are probably minibrains-clumps of neurons that are meant to mimic the way cells fire in a full-grown brain to a very limited extent. Debates have raged over whether these tiny blobs could ever be conscious, feel pain, or think-and over whether they should be called minibrains" at all, given how far removed they are from a fully developed human brain.

We are arguably a long way off from transplanting miniature brain blobs into people (although some have tried putting them in rodents). But we are getting closer to implanting other organoids-potentially those that resemble lungs, livers, or intestines, for example.

The latest progress has been made by Mirian Romitti at the Universite libre de Bruxelles in Belgium and her colleagues, who have successfully created miniature, transplantable thyroids from stem cells.

The thyroid is a butterfly-shaped structure in the neck that makes hormones. A lack of these hormones can make people very sick. Around 5% of people have an underactive thyroid, or hypothyroidism, which can lead to fatigue, aches and pains, weight gain, and depression. It can affect brain development in children. And those who are affected often have to take a replacement hormone treatment every single day.

Transplanting organoids

After growing thyroid organoids in a lab for 45 days, Romitti and her colleagues could transplant them into mice that were lacking their own thyroids. The operation appeared to restore the production of thyroid hormones, essentially curing the animals' hypothyroidism. The animals were very happy," as Romitti puts it.

The focus is now on finding a way to safely transplant similar organoids in people. There is plenty of demand-Romitti says her colleague is constantly getting calls and emails from people who are desperate to get a transplanted mini thyroid. But we're not quite there yet.

Romitti and her teammates made their mini thyroids from stem cells-cells in a naive," flexible state that can be encouraged to form any one of many cell types. It has taken the scientists a decade of research and multiple attempts to find a way to get the cells to form a structure that looks like a thyroid. The end result required genetic modification using a virus to infect the cells, and the team used several drugs to aid the growth of the organoids in a dish.

The stem cells the team used were embryonic stem cells-from a line of cells that were originally taken from a human embryo. These cells couldn't be used clinically for several reasons-the recipient's immune system would reject the cells as foreign, for example, and the destruction of embryos for disease treatments would be considered unethical. The next step is to use stem cells generated from a person's own skin cells. In theory, mini organs created from these cells could be custom-made for individuals. Romitti says her team has made promising" progress.

Of course, we'll also have to make sure these organoids are safe. No one knows what they are likely to do in a human body. Will they grow? Shrink away and disappear? Form some kind of cancer? We'll need more long-term studies to get a better idea of what might happen.

But plenty of scientists, including Romitti, are optimistic. If we can find a way through the ethical and scientific hurdles, even brain organoids could potentially be used to treat disease. The clumps of cells might help to regenerate brain tissue damaged by an injury or stroke, for example. Organoids that can make brain chemicals like dopamine might be useful in treating Parkinson's disease.

To read more about the promise and perils of organoids, check out the following from MIT Technology Review's archive:

1 My colleague Rhiannon Williams recently wrote about the use of teeny-tiny caps to measure the electrical activity of minibrains.

2 During the height of the pandemic, Antonio Regalado explored how lab-grown mini lungs were being used to study how covid-19 kills.

3 This piece, by Russ Juskalian, describes how Madeline Lancaster-a leader in the field-makes brain organoids.

4 And some believe that customized organoids could be used as avatars" for people, to test which drugs might work for them, as Antonio Regalado explains.

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