Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence

Abstract

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI.

Stem-cell therapy in stress urinary incontinence: A review

“…Immunohistochemistry showed thickening of the inferior muscularis in urethral mucosa, which may contribute to sphincter function improvement. Other methods include urethrolysis, pubourethral ligament dissection, urethral sphincterectomy in old multiparous female animals, transgenic animals, and knockout animals [ 30 ]. Muscle precursor cells were injected, and functional sphincter recovery was noted after transplantation in a large animal model (nonhuman primate model) [ 31 ].…”

Effects of Age and Multiple Vaginal Births on Lower Urinary Tract Structure and Function in Nonhuman Primates

“…To advance treatments for SUI, suitable animal models of lower urinary tract disorders mimicking the underlying pathology of SUI in women are desirable. Several animal models have been described, including simulated childbirth, sphincter muscle removal, and direct damage to the pudendal innervation [ 7 , 8 ]. Vaginal distension models are used to mimic childbirth injury and the results of stretch-induced trauma to the urethra, vagina, and pelvic floor [ 8 ].…”