176 Intravenous Mesenchymal Stem Cells Home to the Urethra and Facilitate Recovery From Stress Urinary Incontinence After Childbirth Injury via Local Secretion of Paracrine Factors

Dissaranan, Charuspong; Cruz, Michelle A.; Gill, Bradley; Salcedo, Levilester; Cotleur, Anne C.; Mendieta, Raul; Balog, Brian; Kiedrowski, Matt; Penn, Marc S.; Goldman, Howard; Damaser, Margot

doi:10.1016/j.juro.2011.02.245

Cited by 6 publications

(13 citation statements)

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“…suggested that the pelvic organs might not be the only sites at which stem cell homing occurs upon simulated childbirth injury. 45 In this study, a significant number of stem cells were also identified in the spleens of rats with VD. The study authors speculated that systemically injected cells might modulate the immune system via the spleen.…”

Section: Key Advances In Urological Stem Cell Therapymentioning

confidence: 51%

“…In a rat model of postpartum SUI, we have shown that administering either a systemic injection of BMSCs or a concentrate of the conditioned media (CCM) produced in vitro results in functional and histologic improvements compared to controls. 45 Our data, suggest that paracrine secretions have an important role in the recovery process. A key function of stem cells might thus relate to stem cell homing to areas of injury to stimulate the local secretion of bioactive factors.…”

Section: Stem Cell Therapy For Voiding Dysfunctionmentioning

confidence: 57%

“…reported similar results with BMSCs in response to simulated human childbirth injury. 45 A cardiology study illustrated this point by injecting BMSCs into the hamstrings of hamsters with heart failure. 60 Although cells were unable to migrate out of the muscle, they had significant functional and histological benefit to the heart.…”

Section: Key Advances In Urological Stem Cell Therapymentioning

confidence: 99%

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Stem cell therapy for voiding and erectile dysfunction

et al. 2012

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Voiding dysfunction comprises a variety of disorders, including stress urinary incontinence and overactive bladder, and affects millions of men and women worldwide. Erectile dysfunction (ED) also decreases quality of life for millions of men, as well as for their partners. Advanced age and diabetes are common comorbidities that can exacerbate and negatively impact upon the development of these disorders. Therapies that target the pathophysiology of these conditions to halt progression are not currently available. However, stem cell therapy could fill this therapeutic void. Stem cells can reduce inflammation, prevent fibrosis, promote angiogenesis, recruit endogenous progenitor cells, and differentiate to replace damaged cells. Adult multipotent stem cell therapy, in particular, has shown promise in case reports and preclinical animal studies. Stem cells have also enabled advances in urological tissue engineering by facilitating ex vivo construction of bladder wall and urethral tissue (using a patient's own cells) prior to transplantation. More recent studies have focused on bioactive factor secretion and homing of stem cells. In the future, clinicians are likely to utilize allogeneic stem cell sources, intravenous systemic delivery, and ex vivo cell enhancement to treat voiding dysfunction and ED.

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Section: Key Advances In Urological Stem Cell Therapymentioning

confidence: 51%

Section: Stem Cell Therapy For Voiding Dysfunctionmentioning

confidence: 57%

Section: Key Advances In Urological Stem Cell Therapymentioning

confidence: 99%

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Stem cell therapy for voiding and erectile dysfunction

et al. 2012

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“…13 Such molecular responses to hypoxia and tissue damage have potential as targets for regenerative therapies. 22 …”

Section: Injury Of the Neuromuscular Continence Mechanism: Basic Sciementioning

confidence: 99%

“…A potential alternative treatment with stem cells delivered intravenously, has also shown promise in urological sphincteric and neural injuries with the stem cells homing to both nerve and muscles to facilitate electrophysiological and functional recovery. 22,44 …”

Section: Regenerative Treatments For Stress Urinary Incontinencementioning

confidence: 99%

Stress Incontinence in the Era of Regenerative Medicine: Reviewing the Importance of the Pudendal Nerve

et al. 2013

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Purpose Regenerative medicine will likely facilitate improved stress urinary incontinence (SUI) treatment via restoration of its neurogenic, myogenic, and structural etiologies. Understanding these pathophysiologies and how each can optimally benefit from cellular, molecular, and minimally invasive therapies will become necessary. While stem cells in sphincteric deficiency dominate the regenerative urology literature, little is published on pudendal nerve (PN) regeneration or other regenerative targets. The purpose of this review is to discuss regenerative therapies for PN injury in SUI. Materials and Methods A PubMed® search for pudendal nerve combined individually with regeneration, injury, electrophysiology, measurement, and activity produced a combined but non-independent 621 results. English language articles were reviewed by title for relevance, identifying a combined but non-independent 68 articles. A subsequent Google Scholar® searchand review of references in articles obtained aided in broadening discussion. Results Electrophysiological studies associate PN dysfunction with SUI clinically and assess PN regeneration functionally while animal models provide physiological insight. Stem cell treatment has improved continence clinically while ex vivo sphincteric bulk and muscle function gains have been noted in the laboratory. Stem cells, neurotrophic factors, and electrical stimulation each benefit PN regeneration in animal models. Conclusions Most regenerative work to date focuses on stem cells restoring sphincteric function and bulk, but whether a sphincter denervated by PN injury will benefit is unclear. Regeneration of the PN appears possible through minimally invasive therapies that exhibit significant clinical potential. Treating poor central control and coordination of the neuromuscular continence mechanism remains another challenge.

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Will we ever use stem cells for the treatment of SUI?: ICI‐RS 2011

Goldman

Sievert

Damaser

2012

Neurourology and Urodynamics

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Aims To review the current state of research in the use of stem cells for stress urinary incontinence (SUI) and assess the likelihood of this becoming a relevant treatment option. Methods The peer-reviewed literature consisting of relevant clinical and animal studies on the topic of SUI was surveyed and reviewed. Results Animal studies have demonstrated the potential utility of stem cells in promoting functional recovery of the urethra after simulated childbirth injury. Research in animals suggests similar urethral recovery after injection of bone-marrow derived mesenchymal stem cell secretions as after injection of the stem cells themselves. Therefore, whether the improvements result from the injection of the stem cells themselves or from their secretion of specific proteins is unclear. Early clinical trials have demonstrated the feasibility and short-term safety of injecting muscle-derived stem cells into the urethra to treat SUI. Conclusions Larger and longer term clinical trials are needed. Nonetheless, efficacious stem cell based therapy for the treatment of SUI is practical, achievable and should be available as a treatment modality in the near future.

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176 Intravenous Mesenchymal Stem Cells Home to the Urethra and Facilitate Recovery From Stress Urinary Incontinence After Childbirth Injury via Local Secretion of Paracrine Factors

Cited by 6 publications

References 0 publications

Stem cell therapy for voiding and erectile dysfunction

Stem cell therapy for voiding and erectile dysfunction

Stress Incontinence in the Era of Regenerative Medicine: Reviewing the Importance of the Pudendal Nerve

Will we ever use stem cells for the treatment of SUI?: ICI‐RS 2011

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