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World J Stem Cells. Oct 26, 2021; 13(10): 1564-1579
Published online Oct 26, 2021. doi: 10.4252/wjsc.v13.i10.1564
Current knowledge on the multiform reconstitution of intestinal stem cell niche
Zi-Yan Xu, Jin-Jian Huang, Ye Liu, Yun Zhao, Xiu-Wen Wu, Jian-An Ren
Zi-Yan Xu, Xiu-Wen Wu, Jian-An Ren, Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
Jin-Jian Huang, Ye Liu, Medical School, Southeast University, Nanjing 210009, Jiangsu Province, China
Yun Zhao, Department of General Surgery, BenQ Medical Center, Nanjing 210019, Jiangsu Province, China
Author contributions: Ren JA and Wu XW conceived and commented on this manuscript; Zhao Y and Wu XW approved the manuscript to be published; Huang JJ and Liu Y revised this manuscript; Xu ZY organized the associated literature and wrote this manuscript.
Supported by the 333 High Level Talents Training Project of Jiangsu Province, No. BRA2019011; and Project of Military Research, No. CLB19J025 and No. TGKS2019002.
Conflict-of-interest statement: We declared no potential conflicts of interest with respect to the authorship, and publication of this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian-An Ren, FACS, MD, PhD, Chief Doctor, Professor, Surgeon, Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China. jiananr@gmail.com
Received: July 6, 2021
Peer-review started: July 6, 2021
First decision: July 29, 2021
Revised: August 2, 2021
Accepted: September 15, 2021
Article in press: September 15, 2021
Published online: October 26, 2021
Processing time: 111 Days and 20.4 Hours
Abstract

The development of “mini-guts” organoid originates from the identification of Lgr5+ intestinal stem cells (ISCs) and circumambient signalings within their specific niche at the crypt bottom. These in vitro self-renewing “mini-guts”, also named enteroids or colonoids, undergo perpetual proliferation and regulated differentiation, which results in a high-performance, self-assembling and physiological organoid platform in diverse areas of intestinal research and therapy. The triumphant reconstitution of ISC niche in vitro also relies on Matrigel, a heterogeneous sarcoma extract. Despite the promising prospect of organoids research, their expanding applications are hampered by the canonical culture pattern, which reveals limitations such as inaccessible lumen, confine scale, batch to batch variation and low reproducibility. The tumor-origin of Matrigel also raises biosafety concerns in clinical treatment. However, the convergence of breakthroughs in cellular biology and bioengineering contribute to multiform reconstitution of the ISC niche. Herein, we review the recent advances in the microfabrication of intestinal organoids on hydrogel systems.

Keywords: Intestinal organoids; Reconstitution; Stem cell niche; Bioengineering; Hydrogel

Core Tip: Organoid technique results in a high-performance, self-assembling and physiological platform in intestinal research and therapy. Despite the promising prospect of organoids research, their expanding applications are hampered by the canonical culture pattern, which reveals limitations such as inaccessible lumen, confine scale, batch to batch variation and low reproducibility. The tumor-origin of Matrigel also raises biosafety concerns in clinical treatment. The convergence of breakthroughs in cellular biology and bioengineering contribute to the development of biomaterial-based matrix or bioink for intestinal stem cells and incorporation of 3D printing and organ-on-a-chip technique, which may further advance organoid in future pathophysiological studies or functional tissue reconstitution.