Smail Meziani and M. A. Helmrath
Department of Surgery, University of North Carolina Chapel Hill, NC, United States
As the gastrointestinal system is required for absorption and digestion of nutrients as well as the most common site for absorption of numerous medications, models to understand rare and common human diseases are crucial yet lacking. As many diseases are not applicable to animal models, human studies are currently required to test therapies. Development of functional and specific human intestinal tissue would address this major gap by providing; 1. A means to screen specific factors associated with drug and nutrient absorption in healthy intestine. 2. Unlimited access to disease-modeled specific tissue to support studies characterizing common and rare GI diseases. 3. Development of therapies focused on treatment of specific common (including infectious diseases (viral and bacterial) and rare (cystic fibrosis, IBD, celiac) diseases. Our group has recently described robust and efficient methods for directing human pluripotent stem cells (hPSCs) and induced pluripotent stem cells (iPSCs) into an intestinal 3D culture system; that when transplanted efficiently develop into functional human small intestine (Watson et al. Nature Med 2014). Our ongoing studies support the reproducible phenotype over numerous grafts generated from the same human pluripotent stem cell line. Ongoing advances in the model have provided a way to transplant the grafts into the intestinal mesentery that can be incorporated into the lumenal stream of the mouse (Fig. 1). In addition, recent data support our ability to generate a human intestine with an ENS (Fig. 2) Abstract for Daria. Efficient expansion of IPS cells towards functional human intestine will provided potentially unlimited access to growing this tissue to develop human specific assays. Initially focusing on our patients with identified GI diseases.