LAUSANNE — Imagine a brain the size of the tip of a ballpoint pen. Now imagine that this brain can spontaneously generate an electric charge, just like a human brain could. Well, imagine no more because this tiny human brain replica, a so-called mini-brain, actually exists.
Over the past five years, techniques to manufacture these tiny organs called organoids have developed rapidly. Organoids could revolutionize pharmacological research and limit the use of animal testing. And they're about to hit the market for the first time.
It all started with a discovery that earned Shinya Yamanaka and John Gurdon a Nobel Prize in 2012. They found they could reprogram mature cells to become immature “pluripotent” cells that can then develop into any type of tissue in the human body, provided it gets enough stimulation. A three-dimensional organoid can be created from stem cells suspended in a suitable liquid. As the cells used are mature, the method dodges the ethical issues that plague stem cell research from embryos.
Thomas Hartung, a professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore is one of the many researchers in the field of mini-organs. He said he believes that "organoids are the cell cultures of the 21st century. An organoid can tell us more than a simple two-dimensional in vitro cell culture, such as the interaction between cells and an organ's functions. But this remains a negotiation between complexity and feasibility.”
Thomas Hartung, creator of miniature brains, pictured on his computer screen — Photo: Lloyd Fox/ZUMA
Organoids, which don't have the complexity of a real organ, have so far been unable to recreate all the functions of an organ.
Hartung has developed mini-brains just 350 micrometers in size by stimulating pluripotent cells into nerve cells. Deprived of fresh blood, organoid cells have no access to the nutrients and oxygen they need to grow. Since this must be provided from an external environment, it can't reach the inner cell mass. That's why organoids are so small.
While mini-brains don't have the same anatomy as a real brain, they do have part of the same functionality. Cells can communicate with one another just like in a real brain.
Since we can observe stem cells transform into organoids, we can study diseases that result from a development flaw or from the degradation of a specific organ and understand what causes them. A number of studies are being carried out on the brain alone: multiple sclerosis, Alzheimer's and Parkinson's disease. Mini-brains are also being used for research on viral infections and traumas.
A mini-brain study published in the journal Cell on April 22 confirmed that the Zika virus causes microcephaly in fetuses of infected mothers. By infecting mini-brains at different development stages, scientists were able to identify the deficient cells.
Section of a brain organoid — Photo: Madeline A. Lancaster
Cancer cells are hosted in organoids at QGel, a spin-off from the Switzerland-based École Polytechnique Fédérale de Lausanne. Whether they are from the lungs, the colon or the ovaries, each tumor is cultivated on an industrial scale in a specific environment developed by the company.
"With one single biopsy, our technology allows us to cultivate more than 2,000 identical tumors in three dimensions in small test tubes," says Colin Sanctuary, QGel's co-founder. "This makes it possible to compare quickly the efficiency of drugs on these thousands of tumors, each of which represents a mini-patient."
QGel now sells its growth kits for tumorous organoids to other research laboratories.
Each tumor is tested with different versions or combinations of new medicines being developed. While organoids are a quick and profitable tool for pharmacological tests, they could also accelerate the development of personalized medicine over the next few years. "Being able to test potential drugs on a patient's cells would preserve his health while giving him the most efficient treatment," Sanctuary explains.
In the long run, organoids could also remove the need for animal testing. John Frampton, a researcher at the Dalhousie University in Canada, thinks that organoids are still "a long way away from completely replacing animals. They're generally not whole organs. Mini-brains, for example, are just balls of cortical cells and as such don't reflect the complexity of the entire brain."
Moreover, scientists still need to recreate the way drugs reach the brain in real-life conditions. Research projects on organoids are mushrooming to answer those questions.
Hartung doesn't see the new laboratories as competition. "We all benefit from everybody else's experience. We share all our "recipes." Our interest is to drive science forward," he says.