An organoid-based regenerative technique holds promise as a treatment for short bowel syndrome
organoid © MQ-Illustrations ― stock.adobe.com/jp
In the human body, most of the digestion and absorption of food takes place in the small intestine (small bowel). In certain pathological situations, for example when the small intestine becomes blocked or infected or when tumors develop within the organ, it may need to be partly or completely surgically removed. This operation is called a small-intestine resection. An extensive resection can result in nutrients no longer being properly absorbed into the body, a condition that is known as short bowel syndrome (SBS). Symptoms of SBS include diarrhoea, dehydration, and weight loss, and in 50% of SBS cases, patients require the permanent intravenous administration of nutrition. Today, the only treatment for these patients is organ transplantation but the survival rate is low because of a high probability of the organ being rejected (as well as a shortage of donors). Alternative treatment options are much needed.
One such alternative approach currently being explored is based on advances in regenerative medicine―the term refers to the development of methods for regrowing tissue with specific functions or even organs. A breakthrough in this line of research with implications for SBS has now been reported by Shinya Sugimoto from Keio University and his colleagues, who have succeeded in generating a small-intestine-like organ that mimics the food-absorbing capabilities of the small intestine.
The scientists first created organoids from the tissue of the small intestine―the organoids are essentially cultured clusters of small-intestine stem cells. They speculated that when transplanting organoids to the large intestine (also known as the colon, which is located after the small intestine), a 'small intestinalized colon (SIC)' might form that is able to perform (some of) the functions of the small intestine. Experiments on mice showed that indeed, transplanted organoids can reconstitute small-intestine tissue and absorption capabilities. Importantly, the researchers confirmed the formation of villi―small, finger-like protrusions occurring everywhere in the small intestine and playing a key role in the nutrient absorption process.
To test the therapeutic potential of a SIC, the researchers performed experiments on rats. Parts of the rats' small intestines were removed, leading to SBS, after which SICs were created using the rats' large intestines. The scientists observed that intestinal failure in the SBS rats was reduced significantly. The results suggest that the SIC can perform the function of the small intestine and, importantly, that it can remodel its so-called lymphovascular structure. The latter refers to the highly complex structure of vessels carrying blood and other liquids around within the small intestine.
The findings of Sugimoto and his colleagues hold promise for treating SBS, as even a short residual small intestine (as the result of a resection operation) is still a rich enough source for creating organoids and therefore a SIC. In the words of the researchers, "These data provide a proof of principle for the use of intestinal organoids for regenerative purposes, and offer a feasible strategy for SBS treatment."
Published online 21 June 2021
- Shinya Sugimoto, Eiji Kobayashi, Masayuki Fujii, Yuki Ohta, Kazuya Arai, Mami Matano, Keiko Ishikawa, Kentaro Miyamoto, Kohta Toshimitsu, Sirirat Takahashi, Kosaku Nanki, Yoji Hakamata, Takanori Kanai, Toshiro Sato, An organoid-based organ-repurposing approach to treat short bowel syndrome, Nature, 592, 99-104 (2021). | article