The use of autologous skeletal muscle progenitor cells for adjunctive treatment of presumptive urethral sphincter mechanism incompetence in female dogs

Abstract

Background: Urethral sphincter mechanism incompetence (USMI) is a common problem in female dogs, but some dogs fail to achieve continence with standard treatment. Urethral submucosal injection of autologous skeletal muscle progenitor cells (skMPCs) previously has been shown to restore urethral function in a canine model of USMI.

Hypothesis/objective: To determine if urethral submucosal injection of skMPC alters continence in dogs with USMI that had previously failed standard medical management. We hypothesized that the injections would lead to improved continence.

Animals: Fifteen client-owned dogs with USMI that had failed standard medical management.

Methods: Dogs were prospectively enrolled into a single-armed clinical trial. Once enrolled, a triceps muscle of each dog was biopsied; the tissue specimens were digested, cultured, and expanded to 100 million cells before injection into the urethral submucosa using a surgical approach. Continence was assessed at baseline and 3, 6, 12, and 24 months post-injection using continence scores and urethral pressure profilometry.

Results: Median continence scores increased significantly from baseline at 3, 6, 12, and 24 months. Increases were seen in 14 of 15 dogs with 7, 6 or 1 dog achieving scores of 5, 4 or 3, respectively. Additional medication was required to achieve continence in all but 2 dogs.

Conclusions and clinical importance: Urethral submucosal injection of skMPC can be used adjunctively to improve continence in dogs with difficult to manage USMI. The procedure is labor intensive but well tolerated; most dogs will require continued medication to remain continent.

Keywords: canine; regenerative medicine; stem cell; urinary incontinence.

FIGURE 1

Continence scores at baseline and 3, 6, 12, and 24 months after urethral injection of skeletal muscle progenitor cells. Dogs were given additional medications as needed to improve continence. Each dot represents and individual dog.

FIGURE 2

The change in continence scores from baseline at 3, 6, 12, and 24 months after urethral injection of skeletal muscle progenitor cells. Dogs were given additional medications as needed to improve continence. Each dot represents and individual dog.