Sphincter injury is a common cause of anal incontinence. Surgical repair remains the operation of choice, but the outcome is often poor. In this study the ability of injected bone marrow-derived mesenchymal stem cells (MSC) to enhance sphincter healing after injury and primary repair in a pre-clinical model has been investigated.

Rats were divided into three groups. Group A underwent sham operation (control). Group B had sphincterotomy and surgical repair of external (EAS) and internal anal sphincters (IAS), followed by saline injections. Group C underwent sphincterotomy and surgical repair followed by intrasphincteric injections of syngenic MSC. At 30 days, histological analysis and in vitro contractility testing were performed. GFP positive MSC isolated from transgenic rats have been used to track the cells into the injured area.A significant decrease of muscle tissue was observed at the site of repair after sphincter injury. However, in group C, histological examination demonstrated the presence of new muscle fibres than in group B (p<0.05). Moreover, MSC injection improved contractility of both EAS and IAS sphincter strips compared to group B (p<0.05) evoked by electrical field stimulation of the nerves and by a cholinergic agonist. Preliminary results showed the presence of GFP-MSC into the injured area at least one week after injection. In this experimental model, MSC injection improved muscle regeneration and increased contractile function of anal sphincters after injury and repair. Therefore, MSC may represent an attractive tool for treating anal sphincter lesions in humans.