Success of Lab-Grown Colons Could Transform Future Crohn's and Colitis Research
A group of scientists have successfully taken human pluripotent stem cells and generated human embryonic colons. The human embryonic colons were generated in a laboratory and functioned very similarly to natural human tissues when scientists transplanted them into laboratory mice. The researchers who led this study believe it to be the first time that scientists have successfully tissue engineered human colon organoids in this way.
The researchers from Cincinnati Children's Hospital Medical Center published the research results in the medical journal, Cell Stem Cell, on June 22, 2017.
It is hoped that this technological advancement will open the way for unprecedented colon studies. It should allow for the study and evaluation of diseases and conditions in human modeling systems. There is also a possibility that this technology could generate human gastrointestinal tract tissues that can be transplanted into patients.
According to the senior study investigator, the diseases affecting this part of the gastrointestinal tract may include colitis, irritable bowel syndrome, polyposis syndrome, colon cancer, and Hirschsprung’s disease. Since the animal models do not duplicate the processes of the human diseases in the gastrointestinal tract, the ability to study these diseases has been partially limited. Thus, by providing an effective human model, this new system will allow researchers to properly study human diseases and their development.
Using human pluripotent stem cells, embryonic-stage small intestines were grown by one Dr. Wells and his colleagues. Researcher Jorge Munera noted that one of the most difficult parts of the gastrointestinal tract to generate is the human colon. Another obstacle the authors faced was an absence of data on the embryonic development of the colon, which was overcome by taking the developing hindgut tissues out of the animal models and creating a series of genetic and molecular screens.
SATB2 is a protein that binds to DNA. In the nucleus of human cells, it facilitates the structural organization of chromosomes. Authors believed they would be able to generate colon organoids and, in human models, would be able to express the protein since they were able to provide the molecular signals for the regulation of SATB2. According to the authors, this is partly controlled by the posterior HOX.
The team of researchers took colonic organoids from the tissues and transplanted them into mouse models and found that the posterior region enteroendocrine cells were able to make the hormones that could be found in naturally developing human colons.
It was observed that the human colonic organoids started taking on the form, structure, and cellular and molecular properties of a human colon.
Munera said that how the supporting cells and the lining of the cells within the colon work together in response to inflammation can be discovered by exposing human colonic organoids to certain inflammatory triggers. This could offer a better understating of how to treat patients with Crohn’s disease or ulcerative colitis. He also believes that an accurate model of the human micro biome can be provided by using the organoids.
The human colon organoids can be used to grow various parts of the gastrointestinal tract and can even provide a platform that could serve to test new drugs since most of the oral medications are absorbed through the gut.