Scientists have created functioning human intestinal tissue in the laboratory from pluripotent stem cells.
In the study, two types of pluripotent cells were used: human embryonic stem cells and induced pluripotent stem cells. Induced pluripotent stem cells were generated by reprogramming biopsied human skin cells into pluripotent stem cells.
Human embryonic stem cells are called pluripotent because of their ability to become any of the more than 200 different cell types in the human body. pluripotent stem cells can be generated from the cells of individual patients, and therapeutic cells derived from those pluripotent stem cells would have that person’s genetic makeup and not be at risk of rejection. Because induced pluripotent stem cell technology is new, it remains unknown if these cells have all of the potential of human embryonic stem cells. This prompted the researchers to use both induced pluripotent stem cells and human embryonic stem cells in this study so they could further test and compare the transformative capabilities of each.
To turn induced pluripotent stem cells into intestinal tissue, scientists performed a timed series of cell manipulations using chemicals and proteins called growth factors to mimic embryonic intestinal development in the laboratory.
The first step turned induced pluripotent stem cells into an embryonic cell type called definitive endoderm, which gives rise to the lining of the esophagus, stomach and intestines as well as the lungs, pancreas and liver. Next, endoderm cells were instructed to become one those organ cell types, specifically embryonic intestinal cells called a “hindgut progenitors”. The researchers then subjected the cells to what they describe as a “pro-intestinal” cell culture system that promoted intestinal growth.
Within 28 days, these steps resulted in the formation of three-dimensional tissue resembling fetal intestine that contained all the major intestinal cell types – including enterocytes, goblet, Paneth and enteroendocrine cells. The tissue continued to mature and acquire both the absorptive and secretory functionality of normal human intestinal tissues and also formed intestine-specific stem cells.