Stem cell therapy applied for digestive anastomosis: Current state and future perspectives

Abstract

BACKGROUND Digestive tract resections are usually followed by an anastomosis. Anastomotic leakage, normally due to failed healing, is the most feared complication in digestive surgery because it is associated with high morbidity and mortality. Despite technical and technological advances and focused research, its rates have remained almost unchanged the last decades. In the last two decades, stem cells (SCs) have been shown to enhance healing in animal and human studies; hence, SCs have emerged since 2008 as an alternative to improve anastomoses outcomes. AIM To summarise the published knowledge of SC utilisation as a preventative tool for hollow digestive viscera anastomotic or suture leaks. METHODS PubMed, Science Direct, Scopus and Cochrane searches were performed using the key words “anastomosis”, “colorectal/colonic anastomoses”, “anastomotic leak”, “stem cells”, “progenitor cells”, “cellular therapy” and “cell therapy” in order to identify relevant articles published in English and Spanish during the years of 2000 to 2021. Studies employing SCs, performing digestive anastomoses in hollow viscera or digestive perforation sutures and monitoring healing were finally included. Reference lists from the selected articles were reviewed to identify additional pertinent articles. Given the great variability in the study designs, anastomotic models, interventions (SCs, doses and vehicles) and outcome measures, performing a reliable meta-analysis was considered impossible, so we present the studies, their results and limitations. RESULTS Eighteen preclinical studies and three review papers were identified; no clinical studies have been published and there are no registered clinical trials. Experimental studies, mainly in rat and porcine models and occasionally in very adverse conditions such as ischaemia or colitis, have been demonstrated SCs as safe and have shown some encouraging morphological, functional and even clinical results. Mesenchymal SCs are mostly employed, and delivery routes are mainly local injections and cell sheets followed by biosutures (sutures coated by SCs) or purely topical. As potential weaknesses, animal models need to be improved to make them more comparable and equivalent to clinical practice, and the SC isolation processes need to be standardised. There is notable heterogeneity in the studies, making them difficult to compare. Further investigations are needed to establish the indications, the administration system, potential adjuvants, the final efficacy and to confirm safety and exclude definitively oncological concerns. CONCLUSION The future role of SC therapy to induce healing processes in digestive anastomoses/sutures still needs to be determined and seems to be currently far from clinical use.

Novel techniques for the management of esophageal anastomotic leaks

“…One interesting preclinical study that decreased the rate of ALs was performed in an animal model and used gene therapy with recombinant human vascular endothelial growth factor by direct injection of a non-viral plasmid-based delivery system [42] . Furthermore, early clinical and preclinical studies have shown promising results from the peri-anastomotic administration of biologics, such as porcine fibrin sealant [43] , as well as cell therapy, such as autografting stromal cells in fibrin scaffold [44] and mesenchymal stem cells with or without platelet-rich plasma [45,46] .…”

Human Amniotic Membrane Usage from Bench to Bedside in Congenital Defects and Wounds in Paediatric Surgery: A Systematic Review

“…Contrarily, an experimental study showed no advantage of hAM in postoperative adhesion formation following multilayer AM application to colonic defects 53 . A systematic review based on three experimental models described safe and effective anatomical, functional results with less postoperative adhesions in cases of ischemic bowel disease and Colitis in whom the mesenchymal stem cell has been used as local injections, coating of suture material by stem cell or systematic injection 54,55 . These results can be expanded over the neonates who underwent primary ischemic intestinal anastomosis viz cases of multisegmental Necrotizing enterocolitis.…”