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Organoid-based regenerative medicine for inflammatory bowel disease.
Regenerative Therapy ( IF 3.4 ) Pub Date : 2020-01-13 , DOI: 10.1016/j.reth.2019.11.004
Ryuichi Okamoto 1, 2 , Hiromichi Shimizu 2 , Kohei Suzuki 2 , Ami Kawamoto 2 , Junichi Takahashi 2 , Mao Kawai 2 , Sayaka Nagata 2 , Yui Hiraguri 2 , Sayaka Takeoka 2 , Hady Yuki Sugihara 2 , Shiro Yui 1, 2 , Mamoru Watanabe 3
Affiliation  

Inflammatory bowel disease (IBD) consists of two major idiopathic gastrointestinal diseases: ulcerative colitis and Crohn's disease. Although a significant advance has been achieved in the treatment of IBD, there remains a particular population of patients that are refractory to the conventional treatments, including the biologic agents. Studies have revealed the importance of “mucosal healing” in improving the prognosis of those difficult-to-treat patients, which indicates the proper and complete regeneration of the damaged intestinal tissue. In this regard, organoid-based regenerative medicine may have the potential to dramatically promote the achievement of mucosal healing in refractory IBD patients, and thereby improve their long-term prognosis as well. So far, studies have shown that hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) may have some beneficial effect on IBD patients through their transplantation or transfusion. Recent advance in stem cell biology has added intestinal stem cells (ISCs) as a new player in this field. It has been shown that ISCs can be grown in vitro as organoids and that those ex-vivo cultured organoids can be employed as donor cells for transplantation studies. Further studies using mice colitis models have shown that ex-vivo cultured organoids can engraft onto the colitic ulcers and reconstruct the crypt-villus structures. Such transplantation of organoids may not only facilitate the regeneration of the refractory ulcers that may persist in IBD patients but may also reduce the risk of developing colitis-associated cancers. Endoscopy-assisted transplantation of organoids may, therefore, become one of the alternative therapies for refractory IBD patients.



中文翻译:


基于类器官的再生医学治疗炎症性肠病。



炎症性肠病(IBD)由两种主要的特发性胃肠道疾病组成:溃疡性结肠炎和克罗恩病。尽管 IBD 的治疗已经取得了重大进展,但仍然有一部分患者对传统治疗(包括生物制剂)耐药。研究揭示了“粘膜愈合”对于改善那些难以治疗的患者的预后的重要性,这表明受损肠道组织的适当和完整的再生。在这方面,基于类器官的再生医学可能有潜力显着促进难治性IBD患者粘膜愈合,从而改善其长期预后。迄今为止,研究表明造血干细胞(HSC)和间充质干细胞(MSC)通过移植或输血可能对IBD患者产生一些有益作用。干细胞生物学的最新进展使肠干细胞(ISC)成为该领域的新参与者。研究表明,ISC 可以作为类器官在体外生长,并且那些离体培养的类器官可以用作移植研究的供体细胞。使用小鼠结肠炎模型的进一步研究表明,离体培养的类器官可以移植到结肠炎溃疡上并重建隐窝绒毛结构。这种类器官移植不仅可以促进 IBD 患者中持续存在的难治性溃疡的再生,还可以降低患结肠炎相关癌症的风险。因此,内镜辅助类器官移植可能成为难治性IBD患者的替代疗法之一。

更新日期:2020-01-13
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