A University of Cincinnati molecular and developmental biology graduate student has become one of the first people able to answer a peculiar, but fascinating, question: What does a homegrown mini stomach look like?
“They look like little hollow spheres, and under a low power microscope the surface is folded all over itself,” Kyle McCracken said.
McCracken, along with a team of other scientists based in the lab of Dr. James Wells at Cincinnati Children’s Hospital Medical Center, is among the first scientists in history to create 3D stomach tissue from human pluripotent stem cells.
Simply put, a human pluripotent stem cell is a cell that has been tricked into becoming a different cell.
Wells — the principal investigator for the research who is also a professor at UC’s School of Medicine in the pediatrics department — explains that he could take a person’s skin cell, revert it into a stem cell, and then turn that stem cell into a gastric cell — the kind of cell found in the stomach — that is identical to the gastric cells in that same person’s body.
This process of reverting a cell back to its embryonic state is called “reprogramming,” and Wells likens it to wiping the hard drive of a computer.
“You essentially just wipe all the previous information and bring it back to its base state,” Wells said.
This process was globally acknowledged in 2012 when scientists Shinya Yamanaka and Sir John B. Gurdon were jointly awarded the Nobel Prize in Physiology and Medicine for their research into this subject.
These “mini stomachs,” Wells explained, are about the size and shape of a BB gun pellet. Technically, they are called stomach organoids.
The process of a human pluripotent stem cell becoming a 3D stomach organoid takes about five weeks, but being able to actually harness the ability to do this took three years worth of research.
One glaring problem facing this research was the lack of prior knowledge on turning stem cells into gastric cells.
McCracken says they got lucky early on with their hypotheses and were able to render some promising results.
The longest part of the research consisted of figuring out how to grow and sustain these stomach organoids in the long term.
Now that the study is published, the researchers hope it will be a key tool in modeling stomach development, observing stomach disease, and experimenting with different types of treatment for stomach-related illness.
“Now, we can take patients’ cells who have [diseases like cystic fibrosis, diabetes, epilepsy], turn them into stem cells and push [the newly formed stem cell] into lung, or stomach, or intestine cells. Then we can study the disease process as it unfolds,” Wells said.
Essentially, you can experiment on a patient without actually experimenting on them.
After creating a cell that is identical to the cells in a person’s own body, scientists can introduce a disease that the person is suffering from. They can then watch how it spreads and observe the different effects that treatments will have. All of this can be done outside of the patient’s body.
“It really pushes the field of personalized medicine forward,” Wells said. “ … Every patient responds differently to a drug, so if you can predict how they will respond to one or a cocktail of drugs using these cells in a dish, obviously it is a much better way to move forward — as opposed to just shoving drugs at people.”
Wells warmly referred to his work as “disease in a dish” research.
With the discovery of how to generate gastric cells and stomach organoids with human pluripotent stem cells, Wells and McCracken hope that the medical research community will now be able to perform studies on human stomach development and human stomach disease that have never been able to be performed before.
“We have been working on this for a while and I am glad to see our research finally published,” said McCracken.