Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2016; 22(31): 7099-7110
Published online Aug 21, 2016. doi: 10.3748/wjg.v22.i31.7099
Current understanding concerning intestinal stem cells
Shuang Cui, Peng-Yu Chang
Shuang Cui, Peng-Yu Chang, Department of Radiation Oncology, The First Bethune Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Cui S prepared the majority of the writing; Chang PY formed the figures and tables, designed the outline and coordinated the writing of the manuscript.
Supported by National Natural Science Foundation of China, No. 81502751; and No. 81372929.
Conflict-of-interest statement: All authors claim that there are no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Peng-Yu Chang, MD, Department of Radiation Oncology, The First Bethune Hospital of Jilin University, Changchun 130021, Jilin Province, China.
Telephone: +86-431-88783840 Fax: +86-431-88783840
Received: March 27, 2016
Peer-review started: March 28, 2016
First decision: May 12, 2016
Revised: May 21, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: August 21, 2016

In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same.

Keywords: Intestinal stem cell, Cell development, Colorectal cancer

Core tip: Although the specific roles of intestinal stem cells in epithelial homeostasis and regeneration have been explored, the specific markers for identifying intestinal stem cells (ISCs) remain unclear. The reserve pool of intestinal stem cells is located at the 4+ position of crypts, and their biological characteristics are distinct from the intestinal stem cells at the crypt basement membrane. Intestinal stem cells are important cellular sources for initiating colorectal cancers. Managing murine models of ulcerous colitis using colon organoids indicates the therapeutic effects of ISCs.