The Evaluation of Colorectal Anastomotic Leak and Novel Prevention Strategies

Experimental strategies to reduce the incidence of anastomotic leak (AL) have failed to establish efficacy when translated into clinical practice. There is an increasing interest in the use of stem cell therapies with a focus on the potential repair capability of mesenchymal stem cells (MSCs). However, there remains uncertainty around the fundamental mechanistic process of bowel healing. It is hypothesised that a novel source of MSCs, derived from omentum harvested at laparotomy, can be delivered to an anastomosis to promote healing and prevent AL.

A large scale in-vivo murine study provides a compelling case that the alginate gel delivery vehicle chosen may reduce the severity of anastomotic leak and could provide a practical therapeutic delivery option in humans. The stromal vascular cell fraction is similar across two murine strains, regardless of sex, and contains factors conducive to wound healing. There was a signal that mesenchymal stem cells contained within the stromal vascular cell fraction might reduce anastomotic leak. By combining all the known literature, a novel anastomotic healing model has been developed that provides a way for researchers to investigate the histological changes at the anastomotic line in pre-clinical studies. My findings indicate that healing at the colonic anastomotic line appears to follow the same broad biological steps as documented in the skin healing literature. These findings can now be used to inform pre-clinical testing of other therapeutic interventions for anastomotic leak. My research concludes at the stage where gel/mesenchymal stem-cell-based interventions are ready to be taken into the clinical setting.