When, in the 20th century, cell biologists learned to grow tissue samples in the laboratory, it transformed our understanding of how cells grow and how they react to disease. Crucially, it allowed us to test drug treatments on living cells before risking them in a person.
But tissue samples growing in petri dishes are two dimensional; they are poor substitutes for the solid organs in our bodies. So scientists have recently started coaxing cells to grow in three dimensions. The blobs of tissue they create are called organoids; they are not fully-functioning organs, but nor are they mere sheets of cells. There are organoids of heart, kidney, liver, breast, retina and even brain tissue.
Scientists use organoids to examine organ development and growth and, when investigating diseases such as cancer, the effect of genetic tweaks can be much more easily assessed. The dream, however is to grow organoids in the lab and transplant them into our bodies to replace damaged or diseased tissue. If you have kidney disease, you could get a transplant of a brand new kidney grown from your own tissue. If you have heart disease, you might get healthy new heart tissue. Or if you have a brain injury or degenerative disease such as Parkinson’s or Alzheimer’s, it might even be possible one day to have your brain augmented with a brain organoid.
Now, scientists at Showa University School of Dentistry in Tokyo and the Riken Center for Biosystems Dynamics Research have for the first time successfully grown organoids of salivary glands and transplanted them into mice. The organoids produced saliva like normal glands.
Salivary glands — the things that make your mouth water when you see (or smell) delicious food — are important for digestion and for swallowing, but can be damaged. Kenji Mishima of Showa University says at least 8 million people in Japan suffer from “dry mouth” condition. “We would like to develop a new treatment for severe dry mouth patients using regenerative medicine,” he says.
Mishima, in collaboration with Takashi Tsuji of Riken, took on the challenge of re-creating salivary gland organoids. They grew the tissue from embryonic stem cells — special cells that have the ability to develop into different kinds of tissue in the body.
Once they managed to control the genetic switches that lead to the growth of a salivary gland from a stem cell and tested that the organoid it was very similar to actual salivary glands, Mishima and Tsuji transplanted the tissue into mice that lacked salivary glands. The scientists found that the implanted organoids connected to the mouse’s nerve tissue, and when the mouse was fed they secreted real saliva.
“It was incredibly exciting to see that the tissues we created actually functioned in a living animal,” says Mishima. “This is an important proof of concept that organoids are a valid alternative to actual organs.”
Mishima and Tsuji are now attempting to grow salivary glands from human stem cells. They hope to try transplanting a human organoid in a patient with dry mouth syndrome very soon — perhaps within a year.
Organoids of human brain tissue have already been grown. A Chinese team earlier this year used brain organoids to study the effect of nicotine on brain development. (Their work shows that exposure to nicotine impairs fetal brain development.) A project at the Salk Institute in the United States, also earlier this year, successfully transplanted living organoids of human brain into the brains of mice. The organoid brain tissue continued growing and connected with the mouse brains. OK, it was only tiny blobs of brain tissue implanted into brains the size of the end of your thumb, but it’s a big deal. Imagine when in the near future we start to try similar transplants with humans.
Also consider the ethical issues raised by growing living chunks of brain in the lab. If scientists take your stem cells and use them to grow a brain organoid, is that your brain or theirs? And how big does the brain organoid have to become before you start worrying about its rights?
The field of regenerative medicine is moving fast and is incredibly exciting. It will open the doors to all kinds of advanced treatments, as well as medical ethics questions that people are only just starting to think about. So far, however, the work of Mishima and Tsuji is proving less ethically challenging.
Tsuji, who has worked on ethically “safe” tissues such as hair and skin, says, “We continue to work to develop functional tissues to replace the functions of various organs, and we hope that these experiments will soon find their way into the clinic and help patients suffering from a variety of disorders.”
Rowan Hooper is managing editor of New Scientist magazine. He tweets at @rowhoop and his new book, “Superhuman: Life at the Extremes of Mental and Physical Ability,” is out now.
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