The world of medical research has now entered what we might call its own “Twilight Zone,” an area where we will begin developing and growing not simply organs but cells of many types. Laws that have limited the availability of particular materials for research purposes have prompted this new research, in part. Scientists using incredible creativity and innovative techniques have now advanced their work to the point that they can make small cell bodies trained to play a computer game in a petri dish. If that sounds astonishing, you’re absolutely right, and things will only improve as the research progresses.
Human brain organoids (HBOs) are made in a lab from human stem cells and look and work like parts of the brain. Since it is clearly impossible to study living humans, scientists have been using animal models and cultured neuronal cells to discern how diseases work. However, these methods still have important differences with real brains, such as how they are organized in three dimensions and differences between species, making it hard to study how the higher brain works. These problems can be addressed in a new way with HBO.
In addition to stem cells, researchers have discovered a new source of research material, one that had never been considered in the past; amniotic fluid. During pregnancy, a baby sheds cells into the amniotic fluid surrounding and protecting it.
As a baby grows inside the womb, these cells mix with the amniotic fluid. Now, scientists have shown that they can use those cells to make organoids, which are three-dimensional structures that look and work like human organs. In one case, the organoids were the kidneys, small intestines, and lungs. Organoids might help physicians learn more about how fetal organs are growing, which could lead to earlier detection of birth defects like spina bifida.
It is not the first time organoids have been made from baby cells. Other groups have grown them from baby tissue that was thrown away. But this group is one of the first to make organoids from cells taken from amniotic fluid.
The idea is innovative, and organoids made from fetal fluid have shown it to work. But there is still room for improvement in how you describe the cells that are there.
For many years, scientists have known that fetus cells are in the amniotic fluid. With amniocentesis, a needle is used to take a sample of the fluid. This lets physicians discern conditions like Down syndrome and sickle-cell disease before the baby is born. At least 95% of these cells the baby is shedding are dead.
Organoids made from baby cells have been made before. Other groups have grown them from leftover fetal tissue. On the other hand, one group is the first to make organoids from cells taken from amniotic fluid. It does not affect the baby.
Most people have heard of mini-brains, which are groups of neurons meant to fire in a way similar to how cells fire in a real brain, but not quite. There have been heated arguments about whether these tiny blobs could ever be aware, feel pain, or think, and whether they should even be called “mini-brains” because they differ from a fully developed human brain.
In another area, thyroid disease, a breakthrough may benefit those who suffer from thyroid disease. One study group working on thyroid cells has successfully used stem cells to make tiny thyroids that can be transplanted into mice, but not humans yet.
Hypothyroidism, or an underactive thyroid, affects about 5% of people and can cause tiredness, aches and pains, weight gain, and sadness. It can also change the way children’s brains grow. And people who have it often have to take a treatment every day to replace their hormones. This team’s efforts resulted in getting mice to make thyroid hormones again, which opened the door for humans. About which therapies will work with cancer, there is hope there, too, derived from studies of organoids.
Patient-derived organoids (PDOs) are new and strong pre-clinical models. However, it is still not clear how well they can predict how patients will do in the clinic. What effects will certain treatments have on a patient’s cancer? Organoids made from patients did help predict how well treatment would work for metastatic gastrointestinal cancers.
Researchers also use organoids to study how the host and bacteria interact. Adding immune system parts to infected organoids would be the next step in this direction. A few methods using triple co-cultures have been created, most of which try to replicate harmful illnesses with viruses or bacteria. In all these important research findings, one consideration must be in the mix; ethics with animal brain organoids and simple organoids in dishes.
Until now, these human brain organoids have only been found in test tubes. The most advanced ones are about the size of a pea and pulse with the electrical activity that makes real brains work. In a way that is similar to brains, they make new neurons. They also build the six layers of the human cortex, which is where thinking, speaking, making decisions, and other complex cognitive processes happen.
Many experts in the field do not think an organoid in a dish can think, but we need to talk about this. While we are discovering new ways to combat illness and developmental issues through the use of these organoids, we are also faced with ethical issues all along the way. Each of these issues must be addressed in a way that will benefit everyone and not inhibit the growth of science in its quest for health.
