2021/02/25
Keio University School of Medicine
Japan Agency for Medical Research and Development (AMED)
A joint research group, including Professor Toshiro Sato and Assistant Professor Shinya Sugimoto of The Sakaguchi Laboratory (Organoid Medicine) and Project Professor Eiji Kobayashi of the Department of Organ Fabrication at the Keio University School of Medicine, has developed a technology to create a "small-intestinalized" colon. This is achieved by transplanting small intestinal epithelium, cultured using organoid technology, onto a large intestine that has been stripped of its own epithelium. The resulting organ possesses the unique absorptive and peristaltic functions characteristic of the small intestine.
The small intestine has unique protruding structures called villi, which play a vital role in the digestion and absorption of food. In contrast, the large intestine lacks these structures and is largely incapable of nutrient digestion and absorption. It has long been a mystery why these villous structures form only in the small intestine. The research group has now discovered that the inner epithelium of the small intestine senses the flow of intestinal fluid to create these villous structures, and they have successfully cultured small intestinal epithelial organoids that possess villi. This discovery enabled the development of a technology (small-intestinalized colon technology) to transform the large intestine into a graft that resembles the small intestine. Furthermore, by transplanting a small-intestinalized colon created with this technology into a rat model of short bowel syndrome, the team has provided the world's first demonstration of its therapeutic effect in rats with the syndrome.
Patients who have had a large portion of their small intestine resected due to conditions like Crohn's disease, intestinal volvulus, or severe enteritis during the neonatal period develop short bowel syndrome, a condition with an extremely poor prognosis due to insufficient function for digesting and absorbing proteins, sugars, and lipids. Currently, the only curative treatment for severe short bowel syndrome is small intestine transplantation. However, problems such as a shortage of donors and stronger immune rejection compared to other organs have limited the number of these procedures. In this context, regenerative medicine has been explored as an alternative to transplantation, but creating a complex organ complete with the blood and lymphatic vessels necessary to transport absorbed nutrients throughout the body has been impossible. The small-intestinalized colon technology developed in this study transforms an existing organ into a needed one, bringing us a step closer to realizing rejection-free organ transplantation through regenerative medicine. Furthermore, as this research has shed light on the formation of the small intestine's villous structures, it is expected to contribute to a better understanding of the pathophysiology of various small intestinal diseases.
The details of this research were published in the online edition of the British scientific journal "Nature" on February 24, 2021 (UK time).
For the full press release, please see below.