Applicability of regenerative medicine and tissue engineering for the treatment of stress urinary incontinence in female patients

Abstract

Stress urinary incontinence (SUI) is an age health‐related issue that generates interest due to its considerable public health burden and the controversies surrounding treatment. It is highly prevalent affecting 30–40% of all women during their lifetime. Midurethral slings are the standard of gold standard treatment for female patients with SUI. They have excellent short‐term cure rates; however, their efficacy tends to decrease over time and patients often report urinary incontinence recurrence. This paper addresses the applicability of regenerative medicine and tissue engineering for the treatment of SUI in female patients. Cell‐based treatment with periurethral injection of autologous adipose or muscle‐derived stem cells have been used for SUI; however, the cure rates and SUI recurrence at 1 year were 40% and 70%, respectively. Novel minimally invasive approaches, such as low‐intensity extracorporeal shock wave therapies have shown promising results in SUI animal models. In addition, local injection of growth factors, chemokines, and specific antibodies have shown histological evidence of neoangiogenesis, nerve, and sphincter regeneration in rodents and nonhuman primates with SUI. The use of bioactive factors and proteins secreted by cells, which is called secretomes, have been recognized as key regulators of various mechanisms, such as immunomodulation, angiogenesis, inflammation, apoptosis, and tissue repair. Emerging therapies aiming to replace or restore tissues and organ functionality may improve the long‐term efficacy and in the near future may represent the standard of care for the treatment of SUI.

Combination of PD98059 and TGF-β1 Efficiently Differentiates Human Urine-Derived Stem Cells into Smooth Muscle Cells

“…Both undifferentiated and differentiated stem cells have been used to treat UI [ 28 ]. The different stem cell sources that have been already used include bone marrow, human cord blood, amniotic fluid, and muscle [ 29 ]. Injection of muscle-derived stem cells into the urethra sphincter muscle improved UI-related outcomes [ 30 ].…”

Application of adipose‐derived, muscle‐derived, and co‐cultured stem cells for the treatment of stress urinary incontinence in rat models

“…The therapeutic potential of ADSCs for SUI treatment has already demonstrated positive outcomes regarding muscular tissue regeneration and improving the EUS function by increasing the expression of alpha smooth muscle actin (α‐SMA) and elastin genes and providing the ability of myoblastic differentiation 25,26 . IHC evaluations have revealed that the transplanted cells possess the ability to differentiate into muscle lineages by expressing myoblast progenitor cell markers, angiogenesis, and nerve regeneration; they also found that the cells at the injection site caused a bulge in the lumen of the urethra 15,27,28 . Furthermore, studies indicated that MDSCs, isolated in large quantities, could be employed to significantly raise leak point pressure in SUI animal models as well as to increase muscle contraction, regenerate muscle fiber and blood vessels, and the neuromuscular junction formation 29‐31 .…”

Cell Technologies in the Stress Urinary Incontinence Correction

“…Standard therapies often provide symptomatic relief, but do not target against the underlying etiology, and exhibit tremendous patient-to-patient variability of results, limited success, and procedure-related complications. More clinical trials of new treatment methods involving the required number of patients and with evaluation the long-term results of therapeutic methods for the incontinence correction should be encouraged [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”