New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

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.

Evidence of glucose absorption in a neoformed intestine

“…Although ileal loop vascularization has been preserved, the insufficient blood supply to the midportion of the graft could explain such a shrinkage extent. Other similar reports seem to confirm that a good vascular supply is critical for balanced growth of the neointestine especially at the earliest phase of ABS remodeling [17,22,40,41]. Strictures and important shrinkages were not found in ABS antimesenteric patches, probably because every part of the patch is close to the bowel's intact edges for its whole length and could take advantage of the good vascular supply of the surrounding intestine [24,25].…”

“…Recent advances in the field of tissue regeneration are offering promising therapeutic tools for the treatment of SBS [16,17]. Several reports have described animal models in which the feasibility and efficacy of acellular biologic scaffolds (ABSs) derived from extracellular matrixes of different tissues can promote the growth of neointestine that histologically resembles native intestine [18][19][20][21][22][23][24][25].…”

Duodenocolostomy as Treatment of Ileus in Short Bowel Syndrome: A Case Report

“…This small case series concluded that reestablishment of GI tract continuity after total enterectomy seems to be the best option for postoperative fluid and electrolyte management. Digestive tract restoration can facilitate electrolyte control and dietary support of the patient and can serve as a bridge to newer drug or surgical treatments [ 6 – 8 ], including small bowel transplantation [ 9 ].…”