Effects of human induced pluripotent stem cell-derived intestinal organoids on colitis-model mice

• DOI: 10.1016/j.reth.2022.08.004
• Publication Date: 2022-09-09T10:32:16Z
• Authors: Anna Nakanishi; Satoshi Toyama; Daichi Onozato; Chihiro Watanabe; Tadahiro Hashita; Takahiro Iwao; Tamihide Matsunaga
• Keywords: Organoid

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by repeated remissions and relapses. Immunosuppressive drugs have facilitated the induction maintenance of remission in many patients with UC. However, immunosuppressive cannot directly repair impaired intestinal mucosa are insufficient for preventing relapse. Therefore, new treatment approaches to damaged epithelium UC been attempted through transplantation organoids, which can be differentiated into embedding Matrigel, generated from patient-derived stem cells. The method, however, poses challenge yielding sufficient cells therapy, might already acquired pathological changes. In contrast, human induced pluripotent (iPS) healthy individuals infinitely proliferated target Recently developed iPS cell-derived organoids (HIOs) aim generate that closely resemble adult intestine. no study till date has reported HIOs injected vivo models, it remains unclear whether intestine or retain better ability tissue colitis. We two types via suspension culture without small-molecule compounds: include predominantly more [HIO (A)] those epithelial secretory (B)]. examined engrafted compared their accelerate recovery tissue. Findings showed expressed intestinal-specific markers such as caudal-type homeobox 2 (CDX2) villin, under kidney capsules mice. then colitis-model mice found weight clinical score HIO (A) recovered earlier than sham group. Further, production mucus expression cell proliferation tight junction proteins colon tissues group were restored levels similar observed neither nor (B) could colon. Effective therapy should engraftment at site injury. difference organoid property impacting rate current considered a critical consideration development regenerative medicine using iPS-derived organoids.