Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon (original) (raw)

1. Tomohiro Mizutani1,6,
2. Wakana Mochizuki1,
3. Taichi Matsumoto1,
4. Kengo Nozaki1,
5. Yuriko Sakamaki2,
6. Shizuko Ichinose2,
7. Yukinori Okada3,4,
8. Toshihiro Tanaka3,4,
9. Mamoru Watanabe1 and
10. Tetsuya Nakamura5
11. 1Department of Gastroenterology and Hepatology,
12. 2Research Center for Medical and Dental Sciences,
13. 3Department of Human Genetics and Disease Diversity,
14. 4Bioresource Research Center,
15. 5Department of Advanced Therapeutics for GI Diseases, Tokyo Medical and Dental University, 113-8519 Tokyo, Japan
16. Corresponding author: nakamura.gast{at}tmd.ac.jp
17. ↵6 These authors contributed equally to this study.

Abstract

To develop stem cell therapy for small intestinal (SI) diseases, it is essential to determine whether SI stem cells in culture retain their tissue regeneration capabilities. By using a heterotopic transplantation approach, we show that cultured murine SI epithelial organoids are able to reconstitute self-renewing epithelia in the colon. When stably integrated, the SI-derived grafts show many features unique only to the SI but distinct from the colonic epithelium. Our study provides evidence that cultured adult SI stem cells could be a source for cell therapy of intestinal diseases, maintaining their identity along the gastrointestinal tract through an epithelium-intrinsic mechanism.

• small intestinal stem cell
• transplantation
• stem cell niche
• Paneth cell
• regenerative medicine

Footnotes

• Supplemental material is available for this article.

• Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.245233.114.

• Received May 19, 2014.

• Accepted July 23, 2014.

• © 2014 Fukuda et al.; Published by Cold Spring Harbor Laboratory Press

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