Researchers at the Harvard Wyss Institute have developed a way to effectively culture donor intestinal cells in an organ-on-a-chip device. The technique opens the door to developing personalized medicines for intestinal conditions.
Compared with traditional cell culture techniques, organ-on-a-chip microfluidic devices allow researchers to study physiological processes rapidly, conveniently, and inexpensively. Researchers at the Harvard Wyss Institute have previously developed an intestine on-a-chip device using a cell line originally derived from an intestinal tumor. While the device allowed the research team to study the effects of fluid flow and mechanical stimulation on the intestinal cells, they weren’t able to study patient-specific responses, such as the effect of a drug on the cells of a patient with an intestinal disorder.
To help solve this problem, the Wyss team partnered with researchers at Boston Children’s Hospital to develop a patient-specific intestinal chip. The solution involves using intestinal cells harvested from human volunteers and culturing them as organoids, which are small spherical structures containing a variety of intestinal cells. While organoids are a great method for culturing these cells, they are normally enclosed and covered in a thick extracellular matrix gel, making it difficult to study the effects of drug therapy.
The researchers disrupted the organoids and seeded the cells into their microfluidic chips, but to keep the cells from dying, they developed a method that delivered specialized culture medium over the cells and applied mechanical stimuli to mimic peristalsis in the intestine. The team was able to coax the cells to form an intestinal epithelium with long finger-like extensions, very much like tissue found in the intestine.
The researchers hope that the system could be helpful in testing patient-specific drugs, allowing for personalized drug therapies. “This approach presents a new stepping stone for the investigation of normal and disease-related processes in a highly personalized manner, including the transport of nutrients, digestion, different intestinal disorders, and intestinal interactions with commensal microbes as well as pathogens,” said Donald Ingber, a researcher involved in the study.
Study in Nature Scientific Reports: Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids…