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

To the naked eye, organoids don’t look very appealing. They are essentially tiny blobs. They can look like miniature organs when examined closely. Organoids have been mostly used for research. However, teams have begun transplanting organoids into animals in the hope of curing diseases. Humans are the next step, although they are still a ways 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. There have been many debates about whether these tiny blobs can ever feel pain, think, or be conscious. It is also a matter of whether they should be called “minibrains” given their distance from a fully-developed human brain.

We are still far from transplanting tiny brain blobs into humans ( although some have tried to put 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, a structure that looks like a butterfly in the neck, is responsible for making hormones. People can become very sick if they lack these hormones. Hypothyroidism is a condition in which around 5% of people have an underactive or hypothyroid thyroid. This can cause fatigue, aches, pains, weight gain and depression. It can affect brain development in children. People who are affected must take a replacement hormone treatment each 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 restored the production of thyroid hormones in the animals, effectively curing hypothyroidism. Romitti says that the animals were “very happy”.

The focus now is on safely transplanting similar organoids into people. There is a lot of demand. Romitti says that her colleague receives a lot of emails and calls from people who want to transplant a mini thyroid. We’re not there yet.

Romitti and her colleagues made their mini thyroids using stem cells. These stem cells are in a “naive,” flexible condition that can be encouraged or discouraged to form any type of cell. The scientists spent a decade trying to figure out how to get cells to form a structure that resembles a thyroid. The team used several drugs to stimulate the growth of the organoids in a dish and required genetic modification to infect the cells. The stem cells used by the team were embryonic stem cell lines, which were taken from human embryos. These cells cannot be used clinically due to several reasons. The recipient’s immune system might reject the cells as foreign. Also, the destruction of embryos in order to treat disease would be considered unethical. Next, stem cells can be generated from the skin cells of a person. These cells could be used to create mini organs that can be customized for each individual. Romitti claims that her team has made “promising progress.”

Of course, we will also need to ensure that these organoids remain safe. They are not yet known what they might do in a human body. Will they shrink? They will shrink and disappear. To develop some type of cancer? To get a better understanding of what might happen, we will need to do more long-term studies.

But many scientists, including Romitti are optimistic. If we can overcome the scientific and ethical hurdles, even brain organoids might be able to be used to treat diseases. For example, the clumps of cells could help to regenerate brain tissue that has been damaged by injury or stroke. Organoids that are capable of making brain chemicals such as dopamine could be helpful in the treatment of 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 article, by Russ Juskalian describes how Madeline Lancaster, a leader in this 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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