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      Stem-cell therapy for erectile dysfunction

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          Abstract

          Introduction

          Erectile dysfunction (ED) is the most common sexual disorder that men report to healthcare providers, and is the male sexual dysfunction that has been most investigated. Current treatments for ED focus on relieving the symptoms of ED and therefore tend to provide a temporary solution rather than a cure or reversing the cause. Recently, therapies based on stem cells (SCs) have had an increasing attention for their potential to restore erectile function. Preclinical studies showed that these cells might reverse the pathophysiological changes leading to ED, rather than treating the symptoms of ED. This review is intended to provide an overview of contemporary reports on the use of SCs to treat ED.

          Methods

          We made an extensive search for reports on SC-based therapy for the management of ED, published in English between 1966 and 2013, using the search engines SciVerse-sciencedirect, SciVerse-scopus, Google Scholar and Pubmed, with the search terms ‘erectile dysfunction’, ‘stem cells’, ‘multipotent stromal cells’, ‘adipose (tissue) derived stem cells’, ‘bone-marrow derived stem cells’, ‘animal model’, ‘diabetes’, ‘ageing’, ‘Peyronie’s Disease’ and ‘cavernous nerve injury’.

          Results

          Fifty-four papers were identified and contributed, either as an original research report or review thereof, to this review. Several preclinical studies addressed SC-based therapies for the recovery of erectile function caused by a variety of both chronic and acute conditions. Overall, these studies showed beneficial effects of SC therapy, while evidence on the mechanisms of action of SC therapy varied between studies. One clinical trial investigated the short-term effects of SC therapy in diabetic patients with ED. Two more clinical trials are currently recruiting patients.

          Conclusions

          The rapidly expanding and highly promising body of preclinical work on SC-based medicine providing a potential cure for ED, rather than merely symptom relief, is indicative of the increasing interest in regenerative options for sexual medicine over the past decade. Clinical trials are currently recruiting patients to test the preclinical results in men with ED.

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          Most cited references53

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          Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine.

          Stem cells have been long looked at as possible therapeutic vehicles for different health related problems. Among the different existing stem cell populations, Adipose- derived Stem Cells (ASCs) have been gathering attention in the last 10 years. When compared to other stem cells populations and sources, ASCs can be easily isolated while providing simultaneously higher yields upon the processing of adipose tissue. Similar to other stem cell populations, it was initially thought that the main potential of ASCs for regenerative medicine approaches was intimately related to their differentiation capability. Although this is true, there has been an increasing body of literature describing the trophic effects of ASCs on the protection, survival and differentiation of variety of endogenous cells/tissues. Moreover, they have also shown to possess an immunomodulatory character. This effect is closely related to the ASCs' secretome and the soluble factors found within it. Molecules such as hepatocyte growth factor (HGF), granulocyte and macrophage colony stimulating factors, interleukins (ILs) 6, 7, 8 and 11, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), adipokines and others have been identified within the ASCs' secretome. Due to its importance regarding future applications for the field of regenerative medicine, we aim, in the present review, to make a comprehensive analysis of the literature relating to the ASCs' secretome and its relevance to the immune and central nervous system, vascularization and cardiac regeneration. The concluding section will highlight some of the major challenges that remain before ASCs can be used for future clinical applications.
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            NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence.

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              Stem cell paracrine actions and tissue regeneration.

              Stem cells have emerged as a key element of regenerative medicine therapies due to their inherent ability to differentiate into a variety of cell phenotypes, thereby providing numerous potential cell therapies to treat an array of degenerative diseases and traumatic injuries. A recent paradigm shift has emerged suggesting that the beneficial effects of stem cells may not be restricted to cell restoration alone, but also due to their transient paracrine actions. Stem cells can secrete potent combinations of trophic factors that modulate the molecular composition of the environment to evoke responses from resident cells. Based on this new insight, current research directions include efforts to elucidate, augment and harness stem cell paracrine mechanisms for tissue regeneration. This article discusses the existing studies on stem/progenitor cell trophic factor production, implications for tissue regeneration and cancer therapies, and development of novel strategies to use stem cell paracrine delivery for regenerative medicine.
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                Author and article information

                Contributors
                Journal
                Arab J Urol
                Arab J Urol
                Arab Journal of Urology
                Elsevier
                2090-598X
                2090-5998
                12 September 2013
                September 2013
                12 September 2013
                : 11
                : 3
                : 237-244
                Affiliations
                [a ]Laboratory for Experimental Urology, Gene and Stem Cells Applications, Department of Development and Regeneration, University of Leuven, Leuven, Belgium
                [b ]Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA
                Author notes
                [* ]Corresponding author. Tel.: +1 415 476 3800; fax: +1 415 476 3803. tlue@ 123456urology.ucsf.edu
                Article
                S2090-598X(13)00088-0
                10.1016/j.aju.2013.05.005
                4442996
                26558088
                dfdc0882-9e18-4f36-a978-51a6a30d7269
                © 2013 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 17 March 2013
                : 28 May 2013
                : 30 May 2013
                Categories
                Review

                ageing,cavernous nerve injury,diabetes,peyronie’s disease,ed, erectile dysfunction,pd, peyronie’s disease,cni, cavernous nerve injury,rp, radical prostatectomy,cc, corpus cavernosum,pde5 (i), phosphodiesterase type 5 (inhibitor),no, nitric oxide,(e)(n)nos, (endothelial) (neuronal) no synthase,(a)(e)(h)(m) sc, (adult) (embryonic) (haematopoietic) (mesenchymal) stem cell,ad, adipose tissue-derived,bm, bone marrow-derived,md, muscle-derived,svf, stromal vascular fraction,mpg, major pelvic ganglion,gfp, green fluorescent protein

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