英国弗朗西斯·克里克研究所Vivian S. W. Li和伦敦大学Paolo De Coppi团队合作发现，可利用肠道衰竭患者的类器官来设计可移植的空肠黏膜移植物。这一研究成果于2020年9月7日发表在《自然-医学》上。

研究人员使用来自儿科患者的生物材料构建了自体空肠粘膜移植物，并可以在体外有效形成患者来源的类器官。同时，研究人员利用完整的纳米形貌学获得了无细胞的人肠基质，其可形成生物支架。蛋白质组学和拉曼光谱分析证明了人小肠和结肠支架高度相似的生化特征，表明它们可以作为互换的肠工程平台。

而且，将空肠类器官植入到任一类型的支架上都可以有效地重建移植物，这些移植物具有几个方面的空肠生理功能，并且在移植到小鼠的肾囊或皮下口袋2周后可形成腔结构。

该发现为肠衰竭儿童使用工程化改造的患者特异性空肠移植提供了概念验证数据，最终有助于恢复营养自主性。

据悉，在小肠解剖或功能丧失后，肠功能衰竭会给儿童带来长期影响。对病人护理的重点是增加功能性肠的长度，特别是空肠，以促进营养独立性。

附：英文原文

Title: Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure

Author: Laween Meran, Isobel Massie, Sara Campinoti, Anne E. Weston, Riana Gaifulina, Lucinda Tullie, Peter Faull, Michael Orford, Anna Kucharska, Anna Baulies, Laura Novellasdemunt, Nikolaos Angelis, Elizabeth Hirst, Julia Knig, Alfonso Maria Tedeschi, Alessandro Filippo Pellegata, Susanna Eli, Ambrosius P. Snijders, Lucy Collinson, Nikhil Thapar, Geraint M. H. Thomas, Simon Eaton, Paola Bonfanti, Paolo De Coppi, Vivian S. W. Li

Issue&Volume: 2020-09-07

Abstract: Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for children1. The priority of patient care is to increase the length of functional intestine, particularly the jejunum, to promote nutritional independence2. Here we construct autologous jejunal mucosal grafts using biomaterials from pediatric patients and show that patient-derived organoids can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which forms biological scaffolds. Proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human small intestine and colon scaffolds, indicating that they can be used interchangeably as platforms for intestinal engineering. Indeed, seeding of jejunal organoids onto either type of scaffold reliably reconstructs grafts that exhibit several aspects of physiological jejunal function and that survive to form luminal structures after transplantation into the kidney capsule or subcutaneous pockets of mice for up to 2 weeks. Our findings provide proof-of-concept data for engineering patient-specific jejunal grafts for children with intestinal failure, ultimately aiding in the restoration of nutritional autonomy. In a first step toward developing autologous tissue grafts for the treatment of children with intestinal failure, patient-derived jejunal organoids seeded on scaffolds of decellularized human intestinal matrix formed grafts that had jejunal properties and formed luminal structures when transplanted into mice.

DOI: 10.1038/s41591-020-1024-z

Source: https://www.nature.com/articles/s41591-020-1024-z