Rebuttal to: In Vivo Studies Should Take Priority When Defining Mechanisms of Intestinal Crypt Morphogenesis

Sugimoto, Seiichiro; Sato, Toshiro

doi:10.1016/j.jcmgh.2021.09.010

Cited by 2 publications

(1 citation statement)

References 6 publications

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“…Although much knowledge can be obtained from experiments with mice, studies using human cells are extremely important. 27,28 Unexpectedly, removal of the epithelium also led to new insights into tissue regeneration. The injured area of the epithelium is repaired by the surrounding epithelial cells.…”

Section: Normal Colonic Organoid Transplantationmentioning

confidence: 99%

<i>In Vivo</i> Intestinal Research Using Organoid Transplantation

et al. 2022

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Our understanding of the biology of the intestinal epithelium has advanced since the establishment of an organoid culture system. Although organoids have enabled investigation of the mechanism of selfrenewal of human intestinal stem cells in vitro, it remains difficult to clarify the behavior of human normal and diseased intestinal epithelium in vivo. Recently, we developed a xenotransplantation system in which human intestinal organoids are engrafted onto epithelium-depleted mouse colons. This xenograft recapitulated the original tissue structures. Upon xenotransplantation, normal colon organoids developed normal colon crypt structures without tumorigenesis, whereas tumor-derived organoids formed colonic tumors resembling the original tumors. The non-tumorigenicity of human intestinal organoids highlights the safety of organoid-based regenerative medicine. As an example of regenerative medicine for short bowel syndrome, we devised a unique organ-repurposing approach to convert colons into small intestines by organoid transplantation. In this approach, the transplanted rat small intestinal organoids not only engrafted onto the rat colons but also remodeled the colon subepithelial structures into a small intestine-like conformation. Luminal flow accelerated the maturation of villi in the small intestine, which promoted the formation of a lymphovascular network mimicking lacteals. In this review, we provide an overview of recent advances in gastrointestinal organoid transplantation and share our understanding of human disease biology and regenerative medicine derived from these studies.

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Section: Normal Colonic Organoid Transplantationmentioning

confidence: 99%