对于胃肠道病症，比如克罗恩氏病以及溃疡症等，一般的疗法只能通过药物或者膳食改变来缓解不适的症状，但是如果有一天科学家们开发了一种新型疗法，使用新的肠道组织来替换掉原先炎性的病灶组织，那么对于治疗胃肠道疾病来说将是非常大的进步。
近日，来自布莱根妇女医院等研究机构的研究者通过研究使得肠道干细胞不断生长增殖，进而诱导其分化成为不同类型的成熟肠道组织，相关研究刊登于2013年12月1日发表的美国着名科学杂志《Nature Methods 自然-实验方法》上。
文章作者JeffreyKarp教授表示，使用大量的肠道干细胞就可以帮助治疗那些患有克罗恩氏病等肠道疾病的患者。人类肠道中的隐窝是一种未成熟的成体干细胞，其与帕内特细胞一起生存，隐窝当与帕内特细胞在一起时就会处于未成熟的状态，但是研究者们发现，当帕内特细胞被移除或者被两种细胞信号分子替换时，这些信号分子就会指挥隐窝细胞发育成为特定的肠道干细胞，通过将其它分子引入到干细胞中，最终这种特定的肠道干细胞就会分化成为特殊的成熟肠道细胞。
研究者Xiaolei Yin博士说道，这种方法可以帮助产生大量的相关成熟肠道细胞，这在之前都是不可能实现的；同时也可以使用不同类型的成熟肠道细胞来进行高通量的药物筛选。这项研究可以帮助科学家们进行体内研究来寻找新型分子来帮助清除肠道的损伤组织。
这项研究为研究者将来开发一种新型肠道组织用于治疗肠道疾病患者以及进行安全的药物筛选提供了新的思路和帮助，而且肠道疾病患者也将由此获益。
推荐原文阅读：
Nat Methods. 2013 Dec 1. doi: 10.1038/nmeth.2737. [Epub ahead of print]
Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny.
Yin X, Farin HF, van Es JH, Clevers H, Langer R, Karp JM.
Source
[1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA. [2] Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Cambridge, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4] Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, Massachusetts, USA. [5] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
Abstract
Although Lgr5+ intestinal stem cells have been expanded in vitro as organoids, homogeneous culture of these cells has not been possible thus far. Here we show that two small molecules, CHIR99021 and valproic acid, synergistically maintain self-renewal of mouse Lgr5+ intestinal stem cells, resulting in nearly homogeneous cultures. The colony-forming efficiency of cells from these cultures is ?100-fold greater than that of cells cultured in the absence of CHIR99021 and valproic acid, and multilineage differentiation ability is preserved. We made use of these homogeneous cultures to identify conditions employing simultaneous modulation of Wnt and Notch signaling to direct lineage differentiation into mature enterocytes, goblet cells and Paneth cells. Expansion in these culture conditions may be feasible for Lgr5+ cells from the mouse stomach and colon and from the human small intestine. These methods provide new tools for the study and application of multiple intestinal epithelial cell types.
