The Scarecrow might just get his wish: Scientists try to grow a brain

The Scarecrow might just get his wish. Medical bioengineers are growing neural tissue from scratch.

Medical bioengineering is an area of science that deals with repairing defective tissues and developing “replacement (body) parts” for humans and animals. It’s certainly not a new field. People have tried to replace or modify body parts for centuries. The oldest recorded example is of a toe replacement. An Egyptian mummy was found with an artificial toe in place on its foot. The toe was carved from wood and tied in place with a string.


Teeth have also been replaced by prostheses for hundreds of years. But over that past dozen or so years, medical bioengineering has undergone some radical transformations using computers, new technology and tissue production from stem cells.

Joints, hands, eyes

Some workers in this area design prostheses from metal, plastic, latex and other materials. When joints are replaced, metal prosthetic ones get substituted. Or they may form a fairly natural-feeling and -appearing prosthetic breast for a woman who has undergone a mastectomy. Many other body parts are available to act as structural and cosmetic replacements. There are mechanical hands that can be implanted that allow the wearer to actually make the fingers move and perform complex operations like picking up a cup without crushing it. There is an eye-substitute that is ready to begin clinical trials that can restore sight to some blind individuals by bypassing the damaged or diseased eye and sending impulses directly to the visual cortex in the brain.

Skins, ears, tracheas, hearts


Other medical biomechanical engineers work on the cellular and tissue levels. Helping to prepare cell lines that can be used to grow more natural parts. For example, development, preparation and storage of human skin for later transplant. Bone banking. Cryopreservation of tissues. Growing tissue replacements in the lab. And doing many other exciting things on the edge of this field. Like growing replacement ears from human cells that can be used to replace ears lost to injury, disease or removed surgically. Researchers have grown a human trachea (windpipe) from the patient’s own stem cells and have implanted it into him to replace his own, cancerous trachea.

While all of these are incredibly exciting and complex, real triumphs of creativity and research, there is still more in the pipeline.

While growing a trachea is a major accomplishment, the trachea’s basic structure and function is simple – it’s an air-transporting tube. It doesn’t have the same complexity as a heart, for example. However, researchers are working on building new animal hearts from animal stem cells. A team of researchers has taken rat hearts, digested them down to their underlying framework and then remanufactured a functional heart by engrafting it with cells taken from adult rats. The heart is definitely more complex than the trachea.

But can they grow a brain?

But how about an organ that’s really complex? Something that performs thousands of functions using billions of cells, that are auto regulated. An organ that controls itself and other areas of the body. One of staggering complexity? Something like the brain.

Embryonic stem cells (source: Follow the Money – The Politics of Embryonic Stem Cell Research. Russo E, PLoS Biology Vol. 3/7/2005, e234. doi:10.1371/journal.pbio.0030234 - Images: Nissim Benvenisty)

Embryonic stem cells (source: Follow the Money – The Politics of Embryonic Stem Cell Research. Russo E, PLoS Biology Vol. 3/7/2005, e234. doi:10.1371/journal.pbio.0030234 – Images: Nissim Benvenisty)

With its myriad of functions: emotions, temperature regulation, hormone production, memory, motor control, thought and other processes. Much too complex to build biomechanically? Maybe not. A “cerebral organoid” has been developed that resembles an embryonic brain to an extent.

Researchers used human pluripotent stem cells and incubated them on a medium that resembled the structural substrate of a normal brain. After some initial growth occurred, the cell clumps were placed in a liquid nutrient broth that also supplied oxygen. The proto-brains continued to grow finally reaching the size of a pea (about 4-5 mm in diameter). Several different cell types formed in the new neural tissue as they would in an embryonic developing brain. Some cell types migrated to different areas of the organoid, somewhat as they would in a developing brain. On stained microscopic sections, the brain areas seemed to be able to interact with each other. However, they didn’t form the exact same regions that would be formed in a normally developing brain.

Researchers think that in the embryo and fetus, chemical signals from other fetal tissues cause some changes and cell migration in the brain. Without this chemical signals, these proto-brains didn’t develop properly. Also, these tissue clumps were unable to develop blood vessels. Therefore, growth beyond pea-size was probably impossible because oxygen and nutrients can only diffuse so far into a tissue mass. Additionally, blood vessels can secrete growth factors. Had vessels been present from the beginning, perhaps the neural cells would have formed more normal groups. But, for even as far as the brain architecture progressed, the photos of immunologically stained brain layers are amazing.

Further work is, of course, necessary. With additional manipulations (getting a blood supply to form, adding other tissue factors that would be found in embryos, etc) these cerebral organoids may progress to much more functional neural tissues that can grow, develop and function normally.

Pro-brains might help research on Alzheimer’s, eventually replace damaged brain tissue

If they do so, what would these new brains be good for? Many diseases of the brain, especially degenerative ones like Alzheimer’s, are incredibly difficult to study. These proto-brains might make it easier to look a the pathology of degenerative brain diseases in the lab and possibly come up with a cure. And, since these tissues can be grown from anyone’s stem cells, they would be able to serve as a replacement for damaged brain tissue. For example, a patient who has had a traumatic brain injury or has suffered a stroke has areas of damaged and non-functional tissue. The damaged areas might be able to be replaced with newly grown brain tissue.

Many more years of work still need to be done before we could get anywhere near to doing brain repair in this manner. Of course, it all sounds like an impossibility right now. But how many people thought, just 30 years ago, that we’d even be able to actually grow blobs of brain in a lab?

Mark Thoma, MD, is a physician who did his residency in internal medicine. Mark has a long history of social activism, and was an early technogeek, and science junkie, after evolving through his nerd phase. Favorite quote: “The most exciting phrase to hear in science... is not 'Eureka!' (I found it!) but 'That's funny.'” - Isaac Asimov

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