Adipose tissue-derived stem cell therapy for prevention and treatment of erectile dysfunction in a rat model of Peyronie's disease

Gökçe, Ahmet; Elmageed, Zakaria Y. Abd; Lasker, George F.; Bouljihad, Mostafa; Kim, H.; Trost, Landon; Kadowitz, Philip J.; Abdel‐Mageed, Asim B.; Sikka, Suresh C.; Hellstrom, Wayne J.G.

doi:10.1111/j.2047-2927.2013.00181.x

Cited by 79 publications

(63 citation statements)

References 29 publications

(33 reference statements)

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“…Alternative nonsurgical treatments are continuously being investigated. Recently, intralesional decorin (proteoglycan) 156 and human adipose-derived stem-cell therapy 157,158 have shown promising results in animal models. Further research is needed to determine whether these agents will prove to be safe and effective in humans.…”

Section: Discussionmentioning

confidence: 99%

Peyronie’s Disease: A Review of Etiology, Diagnosis, and Management

Bilgutay

Pastuszak

2015

Curr Sex Health Rep

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Peyronie’s Disease (PD) is a superficial fibrosing disorder of the penis resulting in plaque formation and penile deformity. Once considered rare, PD has more recently been found in up to 13% of men, and can negatively affect sexual and psychosocial function of both patients and their partners. While the etiology of PD is unclear, it is thought to result from an inciting traumatic event followed by aberrant fibrosis or dysregulated wound healing. The evaluation of men presenting with PD includes a detailed history and physical exam, focusing on the penis in both the flaccid and erect states. PD is often associated with erectile dysfunction (ED), as well as several other comorbidities. Laboratory testing is not needed to diagnose PD, although given the associations between PD and systemic diseases including hypogonadism, diabetes, and cardiovascular disease, screening and work-up for these conditions in men with PD may be warranted. Treatment modalities for PD are diverse and include oral, topical, intralesional, mechanical, and surgical therapies. Oral, topical, and mechanical therapies generally have little evidence supporting their efficacy. Several intralesional therapies, including interferon α2b and collagenase Clostridium hystiolyticum have demonstrated efficacy in the treatment of PD. Surgical treatment, indicated in men with significant, stable deformity, includes plication of the tunica albuginea, plaque incision/excision and grafting, and placement of inflatable penile prosthesis (IPP) with or without additional maneuvers to achieve desired results, and has high success rates.

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Section: Discussionmentioning

confidence: 99%

Peyronie’s Disease: A Review of Etiology, Diagnosis, and Management

Bilgutay

Pastuszak

2015

Curr Sex Health Rep

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“…21,22 Local injection of ADSCs into the tunica albuginea decreased Peyronie's-like changes by decreasing the expression of tissue inhibitors of metalloproteinases (TIMPs) and increasing expression of matrix metalloproteinases (MMPs), which resulted in decreased elastosis and fibrosis. 21,22 Urethral stricture disease and Peyronie's disease have similar fibrotic properties despite involving different anatomic locations. Both conditions are characterized by the formation of fibrous tissue with the same types of collagen.…”

Section: Discussionmentioning

confidence: 99%

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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“…Another study used an identical rat model to examine the use of ADSCs as a preventative option against corporal fibrosis. 32 The study showed that injecting ADSCs at the time of injury (prevention) showed similar improvement in erectile function when compared to conventional methods of stem cell therapy. Increased levels of the antifibrotic enzymes matrix metalloproteinase and decreased levels of the profibrotic enzymes tissue inhibitors of metalloproteinases added insight into the mechanism of action stem cells utilized to reduce corporal fibrosis.…”

Section: Adiposeederived Stem Cellsmentioning

confidence: 92%