Holmberg Fredrik Eo, Seidelin Jakob B, Yin Xiaolei, Mead Benjamin E, Tong Zhixiang, Li Yuan, Karp Jeffrey M, Nielsen Ole H
Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Division of BioEngineering in Medicine, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Cambridge, MA, USA.
EMBO Mol Med. 2017 May;9(5):558-570. doi: 10.15252/emmm.201607260.
Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests that intestinal stem cell transplantation could constitute a novel treatment strategy to re-establish mucosal barrier function in patients with severe disease. Intestinal stem cells can be grown in organoid structures, though only a fraction of the cells contained are stem cells with regenerative capabilities. Hence, techniques to enrich stem cell populations are being pursued through the development of multiple two-dimensional and three-dimensional culture protocols, as well as co-culture techniques and multiple growth medium compositions. Moreover, research in support matrices allowing for efficient clinical application is in progress. culture is accomplished by modulating the signaling pathways fundamental for the stem cell niche with a suitable culture matrix to provide additional contact-dependent stimuli and structural support. The aim of this review was to discuss medium compositions and support matrices for optimal intestinal stem cell culture, as well as potential modifications to advance clinical use in IBD.
炎症性肠病(IBD)的发病率和患病率在全球范围内都在上升;在工业化国家,高达0.5%的人口受到影响,欧洲和北美合计约有420万人患有IBD。在实验性结肠炎模型中的成功植入表明,肠道干细胞移植可能构成一种新的治疗策略,用于在重症患者中重建黏膜屏障功能。肠道干细胞可以在类器官结构中生长,不过其中所含的细胞只有一小部分是具有再生能力的干细胞。因此,正在通过开发多种二维和三维培养方案、共培养技术以及多种生长培养基成分来探索富集干细胞群体的技术。此外,关于支持高效临床应用的支架材料的研究也在进行中。培养是通过用合适的培养基质调节对干细胞生态位至关重要的信号通路来实现的,以提供额外的接触依赖性刺激和结构支持。这篇综述的目的是讨论用于优化肠道干细胞培养的培养基成分和支持基质,以及为推进IBD临床应用而可能进行的改进。