Current Role of Stem Cells in Complex Anorectal Disease

Introduction

Anorectal suppurative disease may manifest itself in an acute or a chronic setting. While anal abscess is the acute manifestation of that disease, anal fistula is the chronic form.

A fistula and abscess may coexist or be associated with atypical internal openings and multiple tracts that result in a complex suppurative process. An anal fistula is a tunnel which connects an internal opening, usually an anal crypt at the base of the columns of Morgagni, with an external opening, usually on the perianal skin.

It may be (1) idiopathic or crypto-glandular (the majority), their exact etiology having not been fully understood. Or (2) associated with or confused with Crohn’s disease, tuberculosis, pilonidal disease, hidradenitis suppurativa, lymphogranuloma venereum, presacral dermoid/rectal duplication, actinomycosis, trauma, foreign bodies and malignancy.

The real incidence of anal fistula is unknown, but there is a male preponderance of the disease. The morbidity associated with complex fistula is high, with patients often suffering from multiple hospital admissions over several years, loss of bowel control or a permanent stoma, or even become permanently incapacitated.

Fistula Classification

Fistulas are classified based on their relation to the anal sphincter as intersphincteric, trans-sphincteric and extrasphincteric They also may be superficial, in which case the tract does not traverse the sphincter complex, or suprasphincteric, which extend from the anal skin into the rectum, also without traversing the sphincter complex.

Complex Crohn’s Disease Fistula Management

Fistulizing Crohn disease involves the anus in one third of patients and may have varied presentations such as abscess, fistula, fissure, ulceration, stricture, and large skin tags. Unlike cryptoglandular fistula, surgery for Crohn fistulas is rarely curative. Treatment options for CD fistula involve symptomatic management, antibiotics, anti-TNFɑ medication, steroids, sphincter-sparing surgery (setons, advancement flaps, temporary stomas) and, more recently, stem cell therapy.

Stem cell therapy

Stem cell therapy emerged in the early 2000s as a new option for patients with complex fistula associated with Crohn’s disease.

Mesenchymal stem cells (MSCs) are non-hematopoietic multipotent cells that can depress immune activation and encourage healing of inflamed tissue. They have been found to hinder dendritic cell formation from monocytes, restrict naïve and memory CD4+ cells, stop T cell activation and encourage proliferation of regulatory T cells.

The administration of MSCs to treat complex perianal fistulas has been shown to have potentially effective results. Multiple studies have been published since 2009, with promising results.

Mesenchymal stem cells injected in fistula tracts can be autologous or allogeneic, derived from adipose or bone marrow cells. The majority of studies are phase I or II clinical trials, with only 3 RCTs having currently published results. There are 3 ongoing trials that may help strengthen the evidence towards the use of MSCs in the treatment of complex anorectal fistula.