Development of Transplant Therapy Gives the Large Intestine Digestive and Absorptive Functions Unique to the Small Intestine －Understanding and developing treatments for short bowel syndrome and other small bowel diseases－
February 25, 2021
Keio University School of Medicine
A joint research team at Keio University has developed a technology for creating a small intestinalized colon (SIC)—a large intestine with absorption unique to the small intestine and peristaltic functions. This was achieved by replacing the native colonic epithelium with ileum-derived organoids. The team was led by Professor Toshiro Sato and Assistant Professor Shinya Sugimoto at the Department of Organoid Medicine, Sakaguchi Laboratory, Keio University School of Medicine, and Project Professor Eiji Kobayashi at the Department of Organ Fabrication, Keio University School of Medicine.
The small intestine has unique hair-like projections called villi, which play an important role in the digestion and absorption of food. In contrast, the large intestine does not have these kinds of protruding structures and can hardly digest or absorb nutrients. It has long been a mystery why these projection structures are created only in the small intestine. In this study, the team found that the epithelium inside the small intestine senses streams of intestinal juice and creates villous structures, and they were successful in culturing a villous small intestinal epithelial organoid. This discovery led to the development of a technology that enables the team to generate a "small intestinalized" colon (SIC) by replacing colon epithelium with small intestinal epithelium using organoid transplantation. By transplanting this SIC into a rat short bowel syndrome model, the team has shown, for the first time, that the SIC has a therapeutic effect on rats with short bowel syndrome.
Patients who have had a large portion of their small intestine removed due to Crohn's disease, intestinal torsion, or severe enteritis in the neonatal period develop short bowel syndrome, and the inability to adequately digest and absorb proteins, sugars, and fats leads to short bowel syndrome with poor outcomes. Intestinal transplantation currently remains the only treatment option for severe short bowel syndrome, but due to the shortage of donors and comparatively strong rejection response, the number of transplants remains low when compared to other organs. And so there has been a need for the development of regenerative medicine as an alternative treatment for small intestinal transplantation, but until now it has been impossible to create complex organs including blood vessels and lymph vessels that carry absorbed nutrients throughout the body. The SIC technology developed in this study transforms a different organ into a needed one and takes us one step closer to rejection-free organ transplantation through regenerative medicine. This study has also elucidated part of the origin of the projection structure of small intestinal villi, which is expected to lead to a better understanding of the pathogenesis of various small bowel diseases.
The results of this research were published in digital edition of the British journal Nature on February 24 (GMT), 2021.