Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Mar 24, 2016; 6(1): 1-9
Published online Mar 24, 2016. doi: 10.5500/wjt.v6.i1.1
New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering
Ali Shirafkan, Mauro Montalbano, Joshua McGuire, Cristiana Rastellini, Luca Cicalese
Ali Shirafkan, Mauro Montalbano, Joshua McGuire, Cristiana Rastellini, Luca Cicalese, Texas Transplant Center, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, United States
Author contributions: All authors equally contributed to this paper and design of the study, literature review, editing and final approval of the final version.
Conflict-of-interest statement: No conflicts of interest to disclose.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Luca Cicalese, MD, FACS, Professor, Texas Transplant Center, Department of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, United States. lucicale@utmb.edu
Telephone: +1-409-7722405 Fax: +1-409-7477364
Received: October 1, 2015
Peer-review started: October 9, 2015
First decision: November 4, 2015
Revised: December 27, 2015
Accepted: January 8, 2016
Article in press: January 11, 2016
Published online: March 24, 2016
Processing time: 169 Days and 10.5 Hours
Abstract

Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option.

Keywords: Bioengineered intestine; Tissue engineered; Scaffolds; Organoids; Stem cells; Intestinal elongation techniques

Core tip: Several methods were used to elongate the short and insufficient segment of intestine in patients suffering short bowel syndrome. These methods include transplantation of an intestinal graft, intestinal elongation, and techniques to create a bioengineered segment of intestine. Innovations in using stem cells, organoid units of intestine and bio-scaffolds allow the modern medicine to engineer segments of functional intestinal tissue in animal models. However, to reach the goal of implanting a fully functional bioengineered intestine in human improvements are still required. This article will review various methods to approach this condition from surgical techniques to elongate the intestine to the application of stem cells and bio scaffolds for creating three dimensional intestinal structure.