An entire system of miniature organs known as "organoids" has been created by scientists at the Wake Forest Institute for Regenerative Medicine. In doing so they have built the world's most sophisticated lab model of the human body.
The whole point of the system is that these tiny organs, or "organoids", can successfully determine if a pharmaceutical product is toxic to the human body or not, which would also help put an end to animal testing. The world of organoids is not completely new, however, the Wake Forest experiment has been dubbed as the "World's Most Sophisticated Lab Model of the Human Body."
Their findings were published in the scientific journal Biofabrication.
Researching and creating new medical drugs
Developing new medical drugs requires a lot of money, time, and sometimes the lives of a great many animals. According to a report published in the American Journal of Gastroenterology, it costs an estimated $868 million to $1.24 billion to develop a drug. It's even more disheartening when drugs that have cost a lot of time, effort, money, and animal lives have to then be pulled off of the shelf, as they can't adequately predict whether or not the substance will be toxic to humans in the longer term. Now, a minute innovation may provide some huge answers.
Researchers from the Wake Forest Institute for Regenerative Medicine and Ohio State University have developed an entire system that replicates human organs in microscopic sizes. Everything from the liver, to the heart, and lungs are able to be recreated in tiny sizes so as to improve pharmaceuticals looking to run tests that currently require petri dishes or animals.
The system was then embedded onto a computer chip.
"We tried to make the organs very much related to how they look inside of you, very similar to how they would look on the macro scale if we were implanting them into you," study co-author Anthony Atala, chair and institute director of the Wake Forest Institute for Regenerative Medicine told Popular Mechanics.
These mini-organs have been dubbed "organoids" and are 3D tissue cultures that are sourced from stem cells. To give an estimation of just how small these are, they range from the size of less than the width of a strand of hair to five millimeters.
This isn't the first time researchers have created organoids in a lab, Atala himself has been working on organoids since the early 2000s. However, this is the first time that they have been able to successfully demonstrate levels of toxicity to humans.
Atala and his team focused on building a system as close to the real human system as possible. For instance, the organoid heart pumps roughly 60 times per minute, similar to the human heart. The human liver contains five major cell types, as does the organoid one.
Once the organoids are grown, the researchers can then run tests on them. This is where animal testing could be eradicated.
Atala mentioned "We can test chemotherapies to see which would work best for a given patient. This is great for personalized medicine." This is a huge step forward in the field of medicine.
How do they create these tiny organs?
Interestingly, the foundations for organoid research can be dated back to 1906, when Ross Granville Harrison first adapted a three-dimensional cell culture method called the "hanging drop" for use in the study of embryonic tissues.
For the uninitiated, Harrison was an American biologist and anatomist who is credited for growing the first artificial nerve tissue culture. His contributions would be the guiding path towards the discovery of the nerve growth factor in the 1950s, a vital building block to our study of stem cells today. Over the past 15 years, though there are still limitations, organs can be grown in a lab, and the field is continuing to innovate.
But how do they do it? Within a laboratory setting, researchers must first isolate small samples of human organs and tissues to ensure that tiny organs have the same functionality. What does this mean? As mentioned above, if you were to create an organoid heart, it would pump at the same rate as a human heart. This is why the world of tiny organs is so exciting.
Other research teams outside Ohio State University and the Wake Forest Institute for Regenerative Medicine have also created organoids. In addition to the miniature lab model of the human body, which is useful for testing drugs, organoids also have the capacity to act as organ replacements.
So what have researchers grown so far?
A pair of compact kidneys
The Center for Regenerative Medicine created a pair of working lab-grown kidney organoids. These organs were then transplanted into rats by researchers. According to the research article where it mentions the study in detail, "Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis."
Transplantable, permanently replaceable kidneys would help address this current problem. To do this, the bioengineered graft would need to have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption, and drainage of urine.
Above all, it would need to be compatible with the recipient, to avoid rejection. Researchers were not only able to create these tiny kidneys and transplant them into rats but on transplanting the kidney, the new organs were able to filter blood and produce urine successfully.
The cutest tiny liver organoids
The MRC Centre for Regenerative Medicine has also made progress in the world of organoids, creating tiny livers. In the study, researchers were able to take liver stems, or hepatic progenitor cells, to regrow damaged livers in mice. How did this work? Researchers extracted stem cells from a group of healthy mice. They then took these cells and had them mature in the lab. Once mature, the cells were transplanted back in the mice without any liver failure. The entire process took about three months.
Creating intestine organoids
Researchers at Cincinnati Children's Hospital Medical Center have grown organoid intestines.
Using pluripotent stem cells, researchers were able to grow human intestinal tissue in the lab. However, compared to other processes mentioned in this article, they did something different. To get the tissue to adopt adult tissue architecture, researchers transplanted the tissue to the kidney of a mouse, where it matured within the animal.
Researchers at Cincinnati Children's Hospital Medical Center hope that this method could ultimately be used for the treatment of gastrointestinal diseases globally.
And, can we grow tiny stomachs?
Yes, we can. Created also by a research team at Cincinnati Children's Hospital Medical Center, researchers have found a way to grow three-dimensional gastric tissue. The process involves taking human pluripotent stem cells and coaxing them into becoming stomach cells. The result? Organoids that were only three millimeters in diameter. Tiny organs like these could be used to study various disease models and their effects on the stomach.
According to the research team, "Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world's population and are largely due to chronic Helicobacter pylori infection.
Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis, and there is no experimental model of the normal human gastric mucosa."
Organoids could eliminate animal testing
The darker side of drug testing usually involves animal testing. For the uninitiated, animal testing often centers around the procedures performed on living animals for the research into basic biology and diseases, assessing the effectiveness of new medicinal products, and testing the health and environmental safety of consumer and industry products.
This can include cosmetics, household cleaners, food additives, pharmaceuticals, and industrial/agrochemicals.
Sadly, animals that are part of these procedures tend to be killed or may even be reused in other experiments. According to the Humane Society International, an estimated 115 million animals are tested on worldwide each year.
As more tiny organs are developed in labs across the world, we will be able to slowly tackle the ethical challenges of animal testing, while creating better and safer drugs for humans. Even more so, the world of organoids is a precursor to the coming age of lab-ready organ transplants.
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