Transforming Growth Factor-β1 Induced Urethral Fibrosis in a Rat Model

Sangkum, Premsant; Gökçe, Ahmet; Tan, Ronny; Bouljihad, Mostafa; Kim, Hogyoung; Mandava, Sree Harsha; Saleem, Sarmad N.; Lasker, George F.; Yafi, Faysal A.; Elmageed, Zakaria Y. Abd; Moparty, Krishnarao; Sikka, Suresh C.; Abdel‐Mageed, Asim B.

doi:10.1016/j.juro.2015.02.014

Cited by 36 publications

(37 citation statements)

References 23 publications

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“…Based on our previously published study, we observed a number of TGF-β1 receptors in both human and rat urethras, and there was a significant increase in collagen type I and III expression following TGF-β1 injection in the same manner as in human urethral stricture specimens. 17 Furthermore, researchers have demonstrated that halofuginone, which is a specific inhibitor of TGF-β1 up-regulation, can prevent urethral fibrosis formation in rat urethra. 31,32 As such, we postulate this animal model to be suitable for our proof-of-concept study to evaluate the effects of ADSC injections.…”

Section: Discussionmentioning

confidence: 99%

“…17 Briefly, each rat was anesthetized with 100 mg/kg ketamine (NWI Veterinary Supply, Boise, ID, U.S.) and 10 mg/kg xylazine (Akorn, Decatur, IL, U.S.) intraperitoneally. The rats were placed in the supine position.…”

Section: Urethral Injection Proceduresmentioning

confidence: 99%

“…The degree of fibrosis was evaluated and described as minimal, mild, moderate, and severe. 17 All sections were reviewed by the same pathologist, who was blinded to the study design.…”

Section: Histologymentioning

confidence: 99%

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Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis

Sangkum

Yafi

Kim³

et al. 2016

CUAJ

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Introduction: We sought to evaluate the therapeutic effect of adipose tissue-derived stem cells (ADSCs) in a rat model of urethral fibrosis. Methods: Eighteen (18) male Sprague-Dawley rats (300-350 g) were divided into three groups: (1) sham (saline injection); (2) urethral fibrosis group (10 μg transforming growth factor beta 1 (TGF-β1) injection); and (3) ADSCs group (10 μg TGF-β1 injection plus 2 x 10 5 ADSCs). Rat ADSCs were harvested from rat inguinal fat pads. All study animals were euthanized at two weeks after urethral injection. Following euthanasia, rat urethral tissue was harvested for histologic evaluation. Type I and III collagen levels were quantitated by Western blot analysis. Results: TGF-β1 injection induced significant urethral fibrosis and increased collagen type I and III expression (p<0.05). Significant decrease in submucosal fibrosis and collagen type I and III expression were noted in the ADSCs group compared with the urethral fibrosis group (p<0.05). TGF-β1 induced fibrotic changes were ameliorated by injection of ADSCs. Conclusions: Local injection of ADSCs in a rat model of urethral fibrosis significantly decreased collagen type I and III. These findings suggest that ADSC injection may prevent scar formation and potentially serve as an adjunct treatment to increase the success rate of primary treatment for urethral stricture disease. Further animal and clinical studies are needed to confirm these results. IntroductionUrethral stricture disease is a scarring process of the urethral mucosa and the surrounding spongy tissue of the corpus spongiosum.1 The reported estimated incidence of urethral stricture disease in an older veterans population is 0.6%.2 The incidence of urethral stricture diagnoses among Medicare beneficiaries was 1.4% in 1992 and 0.9% in 2001, respectively.3 Various modalities are available for the treatment of urethral strictures, including urethral dilatation, direct visual internal urethrotomy (DVIU), and various urethroplasty techniques. The long-term recurrencefree rates after DVIU and urethral dilatation remain quite poor. 4 Urethroplasty remains the standard of care for urethral strictures, but recurrence rates as high as 15.6% have been reported following surgery. 5 Factors predictive of treatment failure are not well-documented. 5 However, long stricture length (>4-5 cm), lichen sclerosus, infectious or iatrogenic etiologies, prior urethroplasty, and failed endoscopic therapy are risk factors of urethroplasty failure.6,7 Current adjunctive treatments that aim to improve treatment outcomes include injection of mitomycin c and steroids. [8][9][10] Results of these different treatment options remain inconsistent and, as such, none of these modalities have been widely adopted.Stem cells have the ability to undergo self-renewal and multilineage differentiation, and to form terminally differentiated cells.11 Furthermore, a number of animal studies have demonstrated that mesenchymal stem cells have antifibrotic properties that can reduce fibrosis in the lung, ki...

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Section: Discussionmentioning

confidence: 99%

Section: Urethral Injection Proceduresmentioning

confidence: 99%

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Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis

Sangkum

Yafi

Kim³

et al. 2016

CUAJ

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“…[21][22][23][24] Besides, TGF-β1 was proven to create fibrosis of the urethra in several animal studies. [25,26] These data may indicate a correlation between platelet counts and TGF-β1 levels.…”

Section: Discussionmentioning

confidence: 84%

The predictive value of platelet to lymphocyte and neutrophil to lymphocyte ratio in determining urethral stricture after transurethral resection of prostate

Gül¹,

Altintas²,

Kaynar³

et al. 2017

Turkish Journal of Urology

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Objective: The pathology of urethral stricture disease is still unclear however progressive inflammation may contribute to the development of urethral stricture. The platelet-to-lymphocyte ratio (PLR) is a new and simple marker that indicates inflammation. In this study we aimed to investigate the predictive value of neutrophil to lymphocyte ratio (NLR) and PLR in patients with urethral stricture who underwent transurethral resection of prostate (TURP). Material and methods:A total of 208 patients who underwent bipolar-TURP were included in this study. Patients who had previously undergone surgery due to any urethral pathology, posterior urethral strictures, previous or ongoing treatment for any cancer, hematologic disorders, presence of an active infection at the time of surgical intervention, and prior blood transfusion were excluded. PLR, NLR and red cell distribution width (RDW) levels were measured. In order to investigate the predictive values of NLR and PLR variables, binary logistic regression analysis was performed. Results:No statistically significant differences were observed between the groups in terms of age, NLR, RDW, prostate size and operative times. Statistically significant differences were presented only in the median PLR-values. For predicting urethral stricture, the optimal cut-off value was 112.5, (sensitivity: 0.84, specificity: 0.64; AUC= 0.762, 95% CI 0.684-0.84). Conclusion:In this study we showed that PLR can be used to determine urethral stricture as a cost-effective, common, and simple biomarker in patients after TURP.Keywords: Inflammation; neutrophil to lymphocyte ratio; platelet to lymphocyte ratio; urethral stricture.Cite this article as: Gül M, Altıntaş E, Kaynar M, Buğday MS, Göktaş S. The predictive value of platelet to lymphocyte and neutrophil to lymphocyte ratio in determining urethral stricture after transurethral resection of prostate. Turk J Urol 2017; 43: 325-9

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“…In a multiinstitutional study Sangkum et al (page 820) developed a reproducible TGF-b1 injection technique to induce urethral fibrosis in the urethra of male rats. 3 In the experimental group TGF-b1 (5, 10 or 25 mg) was injected in each side of the urethral wall. Normal saline infiltration was used in the sham treated group.…”

Section: Transforming Growth Factor-b1 Induced Urethral Fibrosismentioning

confidence: 99%

This Month in Investigative Urology

Andersson¹

2015

Journal of Urology

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Transforming Growth Factor-β1 Induced Urethral Fibrosis in a Rat Model

Abstract: TGF-β1 injection can successfully generate a reproducible rat model of urethral spongiofibrosis. This technique is simple, inexpensive and reproducible. Our series is a proof of concept study. Additional studies in larger animals are needed to further confirm our findings.

Cited by 36 publications

References 23 publications

Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis

Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis

The predictive value of platelet to lymphocyte and neutrophil to lymphocyte ratio in determining urethral stricture after transurethral resection of prostate

This Month in Investigative Urology

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