Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency

Chermansky, Christopher; Tarin, Tatum; Kwon, Dong Duek; Jankowski, Ron; Cannon, Tracy W.; Groat, William C. de; Huard, Johnny; Chancellor, Michael B.

doi:10.1016/j.urology.2003.10.035

Cited by 105 publications

(75 citation statements)

References 12 publications

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“…The beneficial effect of the pentadecapeptide BPC 157 on muscle function (12) is important for the relationship between its effect on muscle injury and sphincter function (62). Given systemically, after complete transection of rat quadriceps muscle, peptide BPC 157 leads to full muscle healing (i.e., function, biomechanic, macroscopy, microscopy, immunohistochemistry) (15).…”

Section: Discussionmentioning

confidence: 99%

Prolonged Esophagitis After Primary Dysfunction of the Pyloric Sphincter in the Rat and Therapeutic Potential of the Gastric Pentadecapeptide BPC 157

et al. 2007

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Abstract. Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 µg / kg, 10 ng / kg, last application 24 h before assessment), or continuously in drinking water at 0.16 µg / ml, 0.16 ng / ml (12 ml / rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH 2 O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg / kg, intraperitoneally, once daily; 0.83 mg / ml in drinking water; 50 mg / kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats.

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Section: Discussionmentioning

confidence: 99%

Prolonged Esophagitis After Primary Dysfunction of the Pyloric Sphincter in the Rat and Therapeutic Potential of the Gastric Pentadecapeptide BPC 157

et al. 2007

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“…To date, treatment avenues for voiding dysfunction and urinary incontinence have focused on this potential to restore function via differentiation to replace injured or diseased tissues such as smooth or striated muscle for urethral sphincter regeneration and urothelial tissue for bladder, urethral, and upper urinary tract reconstruction [Al-Awqati and Oliver, 2002;Chermansky et al 2004b;Cruz et al 2011]. It is thought that MSCs restore function in SUI primarily by their ability to differentiate into multiple cell lineages, with animal studies demonstrating increases in urethral muscle, nerves, and connective tissue following MSC injection [Chermansky et al 2004b;Fu et al 2010;Kim et al 2010;Lin et al 2010]. MSCs have also been induced to differentiate into a smooth muscle phenotype when exposed to conditioned media from smooth muscle cell cultures or when induced with specific myogenic growth factors for application to bladder reconstruction .…”

Section: Stem Cell Differentiationmentioning

confidence: 99%

“…Most research testing novel cell-based therapies for SUI has focused on direct stem cell injection into the urethra with the hope of repairing or regenerating damaged rhabdosphincter tissue [Chermansky et al 2004b;Carr et al 2008;Fu et al 2010;Kim et al 2010;Carr et al 2013;Gotoh et al 2013]. Local injections of MSCs, MDSCs, and ADSCs have all demonstrated efficacy in animal models of either mechanical, nerve, or external urethral sphincter injury, as demonstrated by both anatomic and functional outcomes.…”

Section: Stem Cells For Stress Urinary Incontinencementioning

confidence: 99%

“…Regenerative medicine concepts have emerged as an exciting means of fulfilling this therapeutic void by restoring and maintaining normal function via direct effects on injured or dysfunctional tissues [Furuta et al 2007;Wang et al 2011;Goldman et al 2012;Vaegler et al 2012]. Over the past decade, the use of stem cells has shown promise for a host of urologic disorders including applications in lower urinary tract dysfunction, ureteral and bladder trauma, erectile dysfunction, and renal disease [Al-Awqati and Oliver, 2002;Chermansky et al 2004b ;Bivalacqua et al 2007;Zhuo et al 2013].…”

Section: Introductionmentioning

confidence: 99%

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The potential role of stem cells in the treatment of urinary incontinence

Tran

Damaser

2014

Therapeutic Advances in Urology

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Voiding dysfunction encompasses a wide range of urologic disorders including stress urinary incontinence and overactive bladder that have a detrimental impact on the quality of life of millions of men and women worldwide. In recent years, we have greatly expanded our understanding of the pathophysiology of these clinical conditions. However, current gold standard therapies often provide symptomatic relief without targeting the underlying etiology of disease development. Recently, the use of stem cells to halt disease progression and reverse underlying pathology has emerged as a promising method to restore normal voiding function. Stem cells are classically thought to aid in tissue repair via their ability for multilineage differentiation and self-renewal. They may also exert a therapeutic effect via the secretion of bioactive factors that direct other stem and progenitor cells to the area of injury, and that also possess antiapoptotic, antiscarring, neovascularization, and immunomodulatory properties. Local injections of mesenchymal, muscle-derived, and adipose-derived stem cells have all yielded successful outcomes in animal models of mechanical, nerve, or external urethral sphincter injury in stress urinary incontinence. Similarly, direct injection of mesenchymal and adipose-derived stem cells into the bladder in animal models of bladder overactivity have demonstrated efficacy. Early clinical trials using stem cells for the treatment of stress urinary incontinence in both male and female patients have also achieved promising functional results with minimal adverse effects. Although many challenges remain to be addressed prior to the clinical implementation of this technology, novel stem-cell-based therapies are an exciting potential therapy for voiding dysfunction.

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“…Using MDSCs for tissue engineering application and cell transplantation into animals and patients has verified that these cells are highly efficient for stem cellbased therapies in various tissues including regeneration and repair of skeletal and cardiac muscle, bone, articular cartilage, and peripheral nerve. 8,[11][12][13][14][15][16][17][18][19] However, previous studies have been limited to SASCs isolated from healthy noninjured skeletal muscle, and SASCs from injured muscle have not as yet been characterized.…”

mentioning

confidence: 99%

Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

Xiang

Rathbone

et al. 2011

The American Journal of Pathology

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A wide variety of myogenic cell sources have been used for repair of injured and diseased muscle including muscle stem cells, which can be isolated from skeletal muscle as a group of slow-adhering cells on a collagen-coated surface. The therapeutic use of muscle stem cells for improving muscle regeneration is promising; however, the effect of injury on their characteristics and engraftment potential has yet to be described. In the present study, slow-adhering stem cells (SASCs) from both laceration-injured and control noninjured skeletal muscles in mice were isolated and studied. Migration and proliferation rates, multidifferentiation potentials, and differences in gene expression in both groups of cells were compared in vitro. Results demonstrated that a larger population of SASCs could be isolated from injured muscle than from control noninjured muscle. In addition, SASCs derived from injured muscle demonstrated improved migration, a higher rate of proliferation and multidifferentiation, and increased expression of Notch1, STAT3, Msx1, and MMP2. Moreover, when transplanted into dystrophic muscle in MDX/SCID mice, SASCs from injured muscle generated greater engraftments with a higher capillary density than did SASCs from control noninjured muscle. These data suggest that traumatic injury may modify stem cell characteristics through trophic factors and improve the transplantation potential of SASCs in alleviating skeletal muscle injuries and diseases.

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Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency

Cited by 105 publications

References 12 publications

Prolonged Esophagitis After Primary Dysfunction of the Pyloric Sphincter in the Rat and Therapeutic Potential of the Gastric Pentadecapeptide BPC 157

Prolonged Esophagitis After Primary Dysfunction of the Pyloric Sphincter in the Rat and Therapeutic Potential of the Gastric Pentadecapeptide BPC 157

The potential role of stem cells in the treatment of urinary incontinence

Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

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