Scientists say that they have created functioning human intestinal tissue in the laboratory from pluripotent stem cells. The experiment is detailed in the December 12 online issue of Nature.
“This is the first study to demonstrate that human pluripotent stem cells in a petri dish can be instructed to efficiently form human tissue with three-dimensional architecture and cellular composition remarkably similar to intestinal tissue,” points out James Wells, Ph.D., senior investigator on the study and a researcher in the division of developmental biology at Cincinnati Children’s Hospital.
Dr. Wells and the study’s first author, Jason Spence, Ph.D., a member of Dr. Wells’ laboratory, used human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). iPSCs were generated by reprogramming biopsied human skin cells into pluripotent stem cells. This was done in collaboration with Cincinnati Children’s Hospital researchers Susanne Wells, Ph.D., and Chris Mayhew, Ph.D., co-director of the institution’s Pluripotent Stem Cell Facility.
The researchers used the two different types of pluripotent stem cells to test and compare the transformative capabilities of each. To turn pluripotent stem cells into intestinal tissue, scientists performed a timed series of cell manipulations using chemicals and growth factors to mimic embryonic intestinal development in the laboratory.
The first step turned 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 of those organ cell types, specifically embryonic intestinal cells called hindgut progenitors. The researchers then subjected the cells to what they describe as a prointestinal cell culture system that promoted intestinal growth.
Within 28 days these steps resulted in the formation of 3-D tissue resembling fetal intestine that contained all the major intestinal cell types including enterocytes, goblet, Paneth, and enteroendocrine cells, according to the investigators. 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, they add.
Dr. Wells notes that one important next step is to determine if the intestinal tissue is effective in transplant-based treatments of intestinal diseases such as short bowel syndrome. This approach is first tested in animals in collaboration with co-author Noah Shroyer, Ph.D., and Michael Helmrath, M.D., a transplant surgeon at Cincinnati Children’s Hospital.
The researchers also believe the study’s findings will facilitate studies to design better drugs that are more easily taken up by the body.