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      The good, bad, and the ugly of regenerative therapies for erectile dysfunction

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          Abstract

          Erectile dysfunction (ED) is a common condition which reduces quality of life of both patients and their partners, and is a significant health care expense every year. Although phosphodiesterase type-5 inhibitors are the current first-line treatment for men with ED, they are limited by their on-demand dosing, intolerance, and variable efficacy in complex patient populations such as men with multiple medical comorbidities or ED after pelvic surgery. Regenerative medicine has been introduced and investigated in andrology as an encouraging strategy to restore diseased erectile tissue structure and function. Novel regenerative therapies for ED are controversial but are perceived to offer a durable and safe tissue restorative approach to act as a long-term solution to this cumbersome disease process. Here, we review platelet-rich plasma, amniotic fluid membranes, low-intensity extracorporeal shockwave therapy, and stem cell therapy as regenerative strategies to treat ED. Most of these approaches have preclinical and occasionally clinical data to support their ongoing investigation; however, none of these treatments are currently supported for use in ED patients outside of clinical trials.

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          Mesenchymal stem cells: immune evasive, not immune privileged.

          James Ankrum, Joon Faii Ong, Jeffrey M Karp (2014)
          The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or 'immune privileged'; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-the-shelf therapies consisting of MSCs grown in culture. However, recent studies describing generation of antibodies against and immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be immune privileged. Nevertheless, whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known, and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief 'hit and run' mechanism, protecting MSCs from immune detection and prolonging their persistence in vivo may improve clinical outcomes and prevent patient sensitization toward donor antigens.
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            The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences.

            I A Ayta, J. McKinlay, R J Krane (1999)
            To project the likely worldwide increase in the prevalence of erectile dysfunction (ED) over the next 25 years, and to identify and discuss some possible health-policy consequences using the recent developments in the UK as a case study. Using the United Nations projected male population distributions by quinquennial age groups for 2025, the prevalence rates for ED were applied from the Massachusetts Male Aging Study (MMAS) to calculate the likely incidence of ED. The MMAS has the advantage of being the first study to provide population-based rates rather than rates based on clinical samples. All the projections were age-adjusted. It is estimated that in 1995 there were over 152 million men worldwide who experienced ED; the projections for 2025 show a prevalence of approximately 322 million with ED, an increase of nearly 170 million men. The largest projected increases were in the developing world, i.e. Africa, Asia and South America. The likely worldwide increase in the prevalence of ED (associated with rapidly ageing populations) combined with newly available and highly publicized medical treatments, will raise challenging policy issues in nearly all countries. Already under-funded national health systems will be confronted with unanticipated resource requests and challenges to existing government funding priorities. The projected trends represent a serious challenge for healthcare policy makers to develop and implement policies to prevent or alleviate ED.
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              The MSC: an injury drugstore.

              Arnold I. Caplan, Diego Correa (2011)
              Now that mesenchymal stem cells (MSCs) have been shown to be perivascular in vivo, the existing traditional view that focuses on the multipotent differentiation capacity of these cells should be expanded to include their equally interesting role as cellular modulators that brings them into a broader therapeutic scenario. We discuss existing evidence that leads us to propose that during local injury, MSCs are released from their perivascular location, become activated, and establish a regenerative microenvironment by secreting bioactive molecules and regulating the local immune response. These trophic and immunomodulatory activities suggest that MSCs may serve as site-regulated "drugstores" in vivo. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transl Androl Urol
                Journal ID (iso-abbrev): Transl Androl Urol
                Journal ID (publisher-id): TAU
                Title: Translational Andrology and Urology
                Publisher: AME Publishing Company
                ISSN (Print): 2223-4683
                ISSN (Electronic): 2223-4691
                Publication date (Print and electronic): March 2020
                Publication date (Print): March 2020
                Volume: 9
                Issue: Suppl 2
                Pages: S252-S261
                Affiliations
                [1 ]Department of Surgery, Division of Urology, Western University , London, ON, Canada;
                [2 ]Laboratory for Experimental Urology, Department of Development and Regeneration, University of Leuven , Leuven, Belgium;
                [3 ]Department of Urology, Section of Andrology, Akdeniz University School of Medicine , Antalya, Turkey;
                [4 ]The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine , Baltimore, Maryland, USA
                Author notes

                Contributions: (I) Conception and design: JD Campbell, TJ Bivalacqua; (II) Administrative support: None; (III) Provision of study material or patients: N/A; (IV) Collection and assembly of data: JD Campbell, U Milenkovic, MF Usta; (V) Data analysis and interpretation: JD Campbell, U Milenkovic, MF Usta; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Jeffrey D. Campbell. Department of Surgery, Division of Urology, Western University, London, ON, Canada. Email: jcampb49@ 123456uwo.ca .
                Article
                Publisher ID: tau-09-S2-S252
                DOI: 10.21037/tau.2019.10.06
                PMC ID: 7108995
                PubMed ID: 32257866
                SO-VID: bb90ec12-f454-4c93-bb6b-9479e2a0bf51
                Copyright © 2020 Translational Andrology and Urology. All rights reserved.
                License:

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                Date received : 01 June 2019
                Date accepted : 04 October 2019
                Categories
                Subject: Review Article

                Keywords: erectile dysfunction (ed),low-intensity extracorporeal shockwave treatment,amniotic fluid,chorion grafts,stem cell therapy,platelet-rich plasma
                Data availability:
                Keywords: erectile dysfunction (ed), low-intensity extracorporeal shockwave treatment, amniotic fluid, chorion grafts, stem cell therapy, platelet-rich plasma

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