Current and Future Directions of Stem Cell Therapy for Bladder Dysfunction

Abstract

Stem cells are capable of self-renewal and differentiation into a range of cell types and promote the release of chemokines and progenitor cells necessary for tissue regeneration. Mesenchymal stem cells are multipotent progenitor cells with enhanced proliferation and differentiation capabilities and less tumorigenicity than conventional adult stem cells; these cells are also easier to acquire. Bladder dysfunction is often chronic in nature with limited treatment modalities due to its undetermined pathophysiology. Most treatments focus on symptom alleviation rather than pathognomonic changes repair. The potential of stem cell therapy for bladder dysfunction has been reported in preclinical models for stress urinary incontinence, overactive bladder, detrusor underactivity, and interstitial cystitis/bladder pain syndrome. Despite these findings, however, stem cell therapy is not yet available for clinical use. Only one pilot study on detrusor underactivity and a handful of clinical trials on stress urinary incontinence have reported the effects of stem cell treatment. This limitation may be due to stem cell function loss following ex vivo expansion, poor in vivo engraftment or survival after transplantation, or a lack of understanding of the precise mechanisms of action underlying therapeutic outcomes and in vivo behavior of stem cells administered to target organs. Efficacy comparisons with existing treatment modalities are also needed for the successful clinical application of stem cell therapies. This review describes the current status of stem cell research on treating bladder dysfunction and suggests future directions to facilitate clinical applications of this promising treatment modality, particularly for bladder dysfunction.

Management of Urinary Incontinence With Underactive Bladder: A Review

“…The clinical efficacy and safety of intradetrusor injections of autologous muscle-derived cells for UAB were reported in a pilot study with humans [37]. Stem cells can restore the urethral sphincter function, and several clinical trials have shown the potential of stem cell therapy for managing SUI [38]. Although there is currently insufficient evidence, the application of stem cell therapy to both detrusor smooth muscle and urethral sphincter smooth muscle may be used to treat UAB patients with incontinence.…”

BMMSC-sEV-derived miR-328a-3p promotes ECM remodeling of damaged urethral sphincters via the Sirt7/TGFβ signaling pathway

“…It has been widely reported that stem cells can motivate the ECM reconstruction of the urethral sphincter to promote the recovery of urethral function in SUI [ 13 – 16 ]. Among the stem cells that have been studied, bone marrow mesenchymal stem cells (BMMSC) are the most widely used stem cells in tissue repair and regenerative medicine due to their universal source, self-renewal capacity in vitro, and low immunogenicity.…”

Application of Adult and Pluripotent Stem Cells in Interstitial Cystitis/Bladder Pain Syndrome Therapy: Methods and Perspectives

“…Accordingly, our review discusses the possible approaches for applying stem cells (ASCs and PSCs) in bladder regeneration and IC/BPS therapy, which are summarized in Table 1. Many preclinical studies demonstrate biosafety and the potential of stem cells to treat bladder diseases [221]. As described above, the therapeutic potentials of ASCs and PSCs in bladder regeneration are attributed to their ability to differentiate into key bladder cells, such as urothelium and SMCs.…”