Molecular mechanism of the colonic stem cell niche during intestinal epithelial regeneration in inflammatory bowel disease.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03455
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Gunma University (2021-2022); Keio University (2019-2020)
• Principal Investigator: Sasaki Nobuo 群馬大学, 生体調節研究所, 教授 (30777769)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: オルガノイド / 組織幹細胞 / 潰瘍性大腸炎 / 幹細胞ニッチ

Outline of Final Research Achievements

The colonic epithelium has the excellent regenerative capacity. Even though it is usually damaged by inflammation, it initiates various events such as reactivation of Lgr5+stem cells, quiescent stem cells, and plasticity that promote epithelial regeneration. This repair function is impaired in the intestinal epithelium of patients with inflammatory bowel disease, but the nature of this impairment remains unclear. Using both genetically modified mouse model and organoid systems, we found that epithelial niche cells of intestine are the starting cells for regenerating microenvironment disrupted by injury. Those results will identify the regenerative origin cells in inflammation impaired colonic epithelial cells, which are expected to become novel therapeutic target cells for inflammatory bowel disease.

Free Research Field

幹細胞学

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患は難治性疾患の一つであり，一旦寛解しても完治せずに再燃する罹病期間が長期になることが知られている．これまでも治療薬としてステロイドや免疫調節薬などあるが，その全てが効果があるわけでは無い．そこで本研究では炎症障害を受けた腸管上皮細胞の再生メカニズムの分子基盤を明らかにすることで，新しい治療法の開発を目指してきた．本課題研究では，炎症によってダメージを受けた腸管上皮幹細胞の微小環境が再生過程の起点になることを新たに見出した．今後は，この幹細胞微小環境を標的とした粘膜再生治療が炎症性腸疾患の画期的な治療法になることが期待される．