The human intestine participates in a tremendous array of processes that are essential for daily life, including absorption of nutrients, secretion of hormones, and function as an immune organ against bacteria, viruses and parasites. Because of this, diseases of the intestine such as inflammatory bowel diseases, mesenteric ischemia, congenital short gut syndromes and trauma can produce severe disability and even mortality. In extreme cases where the degree of intestinal compromise is extremely severe, patients may need receive all of their nutrition intravenously, or even undergo intestinal transplantation. The purpose of this research is to induce human embryonic stem cells to develop into intestinal derivatives, to provide a replacement tissue these disorders of severe intestinal dysfunction.
The first goal has been to place human embryonic stem cells into a nurturing enviroment, or niche, where they would be exposed to the same signals that intestinal cells receive in the human body. Accordingly, human embryonic stem cells have been injected into cultures of mouse intestine in which such signals are operative. Under these conditions, the embryonic stem cells incorporate adjacent to the mouse intestine as well as to supporting stromal cells, and undergo a dramatic change in morphology, although they do not acquire an intestinal identity. Injections of embryonic stem cells that have been induced to become endoderm, a precursor tissue to the intestine, appear more encouraging. The second goal has examined the ability of stimulation of the Wnt pathway to induce intestinal growth and differentiation of human embryonic stem cells. These studies have confirmed that Wnt pathway stimulation greatly promotes growth of intestinal cultures, suggesting that such a strategy could feasibly promote the differentiation of human embryonic stem cells to become intestine. Finally, the third goal is to develop niches for intestinal differentiation of human embryonic stem cells that are fully comprised of mouse tissue. Here, a variety of strategies of tissue preparation and culture are under evaluation.