Unlimited expansion of intestinal stem cells from a wide range of ages.

Integrative molecular medicine Pub Date : 2019-08-01 Epub Date: 2019-07-15 DOI:10.15761/IMM.1000375
Marcin Duleba, Rajasekaran Mahalingam, Audrey-Ann Liew, Yutao Qi, Rahul Neupane, Matthew Vincent, Suneal Agarwal, Francisco A Sylvester, Jeffrey S Hyams, Khek Yu Ho, Jason K Hou, Frank McKeon, Wa Xian
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Abstract

The recent technical advance in cloning and culturing ground-state intestinal stem cells (ISC) provides us an opportunity of accurate assessment of age-related impact on the function of highly proliferative intestinal stem cells. Our ability of indefinitely and robustly expanding single-stem-cell derived pedigrees in vitro allows us to study intestinal stem cells at the clonal level. Interestingly, comparable number of ISC clones was yielded from 1mm endoscopic biopsy of all donors despite the age. They were passaged in vitro as pedigrees and expanded to 1 billion cells in approximately sixty days without changes in stemness demonstrated by clonogenicity and multipotency. Therefore, our study shows that ISCs from a wide range of ages can be cloned and expanded to unlimited number in vitro with similar efficiency and stability. These patient-derived ISCs harbor intrinsic immortality and are ideal for autologous transplantation, supporting the promise of adult-stem-cell based personalized medicine.

Abstract Image

Abstract Image

来自不同年龄段的肠道干细胞的无限扩增。
最近在克隆和培养基态肠干细胞(ISC)方面的技术进步为我们提供了一个准确评估与年龄相关的对高增殖性肠干细胞功能影响的机会。我们能够在体外无限期、稳健地扩增单干细胞来源的谱系,这使我们能够在克隆水平上研究肠道干细胞。有趣的是,尽管年龄不同,所有捐赠者的1mm内窥镜活检都产生了数量相当的ISC克隆。它们作为家系在体外传代,并在大约60天内扩增到10亿个细胞,而克隆性和多能性显示的干性没有变化。因此,我们的研究表明,来自不同年龄段的ISC可以在体外以类似的效率和稳定性克隆和扩增到无限数量。这些患者来源的ISC具有内在的永生性,是自体移植的理想选择,支持了基于成人干细胞的个性化药物的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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