Adult Stem Cell Therapy of Female Stress Urinary Incontinence

Mitterberger, Michael; Pinggera, Germar-Michael; Marksteiner, Rainer; Margreiter, Eva; Fussenegger, Martin; Frauscher, Ferdinand; Ulmer, Hanno; Hering, Steffen; Bartsch, Georg; Strasser, Hannes

doi:10.1016/j.eururo.2007.07.026

Cited by 120 publications

(89 citation statements)

References 15 publications

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“…To date, only a few studies of stem cell implantation in experimental models of ED, to repair either nerves or smooth muscle in the corpora, have been conducted [20][21][22][23], although stem cells are also being investigated for the repair of other urogenital organs, such as the bladder, urethra, and kidney [24][25][26][27]. The first study in the penis [20] was based on the injection of rat embryonic stem cells modified ex vivo to express brain-derived nerve growth factor into the corpora cavernosa in a rat model of cavernosal nerve damage.…”

Section: Introductionmentioning

confidence: 99%

Effect of muscle‐derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat

et al. 2008

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OBJECTIVETo determine whether skeletal muscle‐derived stem cells (MDSCs) convert into smooth muscle cells (SMCs) both in vitro and in vivo, and in so doing ameliorate the erectile dysfunction (ED) of aged rats, and whether endogenous stem cells are present in the rat corpora cavernosa.MATERIALS AND METHODSMDSCs were obtained from mouse muscle, and shown by immunocytochemistry for α‐smooth muscle actin (αSMA) to originate in vitro in myofibroblasts and SMCs, discriminating SMCs by calponin 1 expression. In vivo these MDSCs, labelled with 4′,6‐diamidino‐2‐phenylindole, were implanted into the corpora cavernosa of young adult (5‐month old) and aged (20‐month old) rats for 2 and 4 weeks. Histological changes were assessed by immunohistochemistry and quantitative Western blot. Functional changes were determined by electrical field stimulation (EFS) of the cavernosal nerve.RESULTSThe exogenous cells replicated and converted into SMCs, as shown in corporal tissue sections by confocal immunofluorescence microscopy for proliferating cell nuclear antigen (PCNA), αSMA, and smoothelin, and also by Western blot for αSMA and PCNA. MDSC differentiation was confirmed by the activation of the αSMA promoter‐linked β‐galactosidase in transfected cells, both in vitro and after implantation in the corpora. Putative endogenous stem cells were shown in corporal tissue sections and Western blots by detecting CD34 and a possible Sca1 variant. EFS showed that implanted MDSCs raised in aged rats the maximal intracavernosal pressure/mean arterial pressure levels above (2 weeks) or up to (4 weeks) those of young adult rats.CONCLUSIONSMDSCs implanted into the corpora cavernosa of aged rats converted into SMCs and corrected ED, and endogenous cells expressing stem cell markers were also found in untreated tissue. This suggests that exogenous stem cell implantation and/or endogenous stem cell modulation might be viable therapeutic approaches for ageing‐related ED.

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Section: Introductionmentioning

confidence: 99%

Effect of muscle‐derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat

et al. 2008

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“…Cure rate probabilities for IVM were estimated based on three different studies. Two studies from Mitterberger et al [16,28], and a third study from Blaganje and Lukanovic [18]. These studies showed cure rates of 90% (n = 20), 79% (n = 119) and 23.7% (n = 38), respectively.…”

Section: Probabilitiesmentioning

confidence: 99%

“…future science group www.futuremedicine.com Probability of mesh erosion following MUS surgery 2.24% [24] Probability of mesh erosion that requires sling revision/excision 84.6% [24] Probability of cure after sling revision/excision 15.4% [24] Probability of SUI after sling revision/excision 36% [25] Probability of sustained SUI after MUS surgery 9.3% Estimated Probability of reoperation with MUS due to sustained SUI 2.4% [6] Probability of having de novo urge incontinence after insertion of MUS 6.4% [26] Probability of receiving anticholinergic medicine as treatment of de novo urge incontinence 16.5% [10] Probability of urinary retention after MUS insertion that requires release 6.01% [10] Probability of persistent SUI after sling release 13% [27] Probability of cure with IVM 68.4% [16,18,28] Probability of persistent SUI after treatment with IVM 31.6% [16,18,28] Probability of cure with MM 25% [15] Probability of persistent SUI after treatment with MM 75% [15] IVM: In vitro myoblast approach; MM: Minced myofiber approach; MUS: Midurethral sling; SUI: Stress urinary incontinence. Health utility value of no incontinence 0.93 [29] Health utility value for SUI 0.71 [29] Health utility value for treatment of de novo urge with anticholinergic medication 0.81 [29] Health utility value for de novo urge after MUS operation 0.74 [29] Health utility value for repeated MUS operation 0.89 [23,29] MUS: Midurethral sling; SUI: Stress urinary incontinence.…”

Section: Probabilitiesmentioning

confidence: 99%

Cell-based Therapy for the Treatment of Female Stress Urinary Incontinence: An Early Cost–Effectiveness Analysis

et al. 2018

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Aim:To perform an early cost-effectiveness analysis of in vitro expanded myoblasts (IVM) and minced myofibers versus midurethral slings (MUS) for surgical treatment of female stress urinary incontinence. Methods: Cost-effectiveness and sensitivity analyses were performed using a decision tree comprising previously published data and expert opinions. Results & conclusion: In the base case scenario, MUS was the cost-effective strategy with a negative incremental cost-effectiveness ratio compared with IVM and a positive incremental cost-effectiveness ratio compared with minced myofibers. However, the sensitivity analysis indicates that IVM may become an alternative providing greater effect at a higher cost. With the possibility of becoming more effective, IVM treatment would be advantageous over MUS given its reduced invasiveness and lower risks of complications. Urinary incontinence (UI) is a common medical condition that has a negative impact on the quality of life of individuals of all ages, racial and ethnic groups. The prevalence of UI is about two-to-four-times higher in women than in men, ranging from 11 to 57% [1]. The most common subtype is stress urinary incontinence (SUI), affecting roughly 50% of any women with UI [2]. SUI describes a condition where there is an involuntary leak of urine when intra-abdominal pressure rises, for example, when coughing, sneezing, laughing or during other physical activity. SUI has not only a severe impact on quality of life but it also places a substantial economic burden on the healthcare system and society [3][4][5]. In the USA, for example, it has been estimated that in 1998, the average direct medical cost of SUI amounted US$5642 per patient, while the indirect workplace expenses were US$4208 [3]. Evidence suggests that these costs have experienced an age-related increase over the last years [5].The clinical management of SUI is complex and may involve conservative treatments, such as pelvic floor muscle training and pharmacotherapy, as well as surgical procedures. Currently, the gold standard for surgical management of SUI in women is the midurethral sling (MUS), which displays a cure rate of 80-95% [6][7][8]. While MUS has a high success rate, 5-20% of the patients will have persisting incontinence thus needing to undergo sling removal and subsequent treatment [9]. The postoperative complications reach as high as 7.2% for erosion and the risk of getting a perioperative urinary tract infection is 17.2% [10]. As an alternative to MUS implantation, with the goal of targeting the underlying etiology rather than relieving the symptoms, cell-based therapies (CBTs) have recently emerged [11]. Among the different modalities of CBT, intraurethral injection of autologous skeletal myoblasts appears as one of the most promising regenerative therapies for SUI [12]. While various large-scale clinical trials are still ongoing, results from the initial clinical studies have shown that these approaches appear to be safe and moderately effective. Remarkably, a recent study has shown ...

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“…[11][12][13][14][15][16] Chancellor et al first examined the effects of MDSC injected into the urethra and bladder wall of a rat, and confirmed the formation of myotubes and myofibers in the smooth muscle layers. 17 In their human clinical application study, Carr et al reported the results from the first North American clinical MDSC therapy trials. 15 According to their report, eight women received injections of pure MDSC obtained from muscle biopsy specimens from the lateral thigh.…”

Section: Urethral Sphinctermentioning

confidence: 99%

Regenerative medicine as a new therapeutic strategy for lower urinary tract dysfunction

Sumino

Mimata

2013

Int J of Urology

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Abbreviations & AcronymsAbstract: The use of regenerative medicine for the treatment of organic and functional disorders intractable to conventional treatment has increased worldwide. This innovative medical field might particularly hold promise for the treatment of lifethreatening diseases or healing of irreplaceable organs, such as the heart, liver and brain. Dysfunction of the urogenital tract and associated organs other than the kidney might not have immediate life-threatening implications; furthermore, the effectiveness of alternative therapy, such as enterocystoplasty for bladder cancer, has been shown. Therefore, most physicians or scientists do not give much importance to these disorders. However, urological disease has increased in developed societies in recent years. Furthermore, medical costs have also escalated. Disorders of the lower urinary tract, such as urinary disturbance or incontinence, can lead to other complications, impairing quality of life and ultimately increasing short-and long-term medical expenses. Regenerative medicine might hold potential solutions to these problems. Recent advances in urogenital regenerative medicine are reviewed in the present article, with particular reference to lower urinary tract reconstruction. The potential of regenerative medicine for the treatment of intractable lower urinary tract dysfunction compared with conventional treatment is also discussed.

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Adult Stem Cell Therapy of Female Stress Urinary Incontinence

Cited by 120 publications

References 15 publications

Effect of muscle‐derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat

Effect of muscle‐derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat

Cell-based Therapy for the Treatment of Female Stress Urinary Incontinence: An Early Cost–Effectiveness Analysis

Regenerative medicine as a new therapeutic strategy for lower urinary tract dysfunction

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