Stem cell treatment of erectile dysfunction ☆ , ☆☆ Amjad Alwaal a,b, ⁎, Uwais B. Zaid a , Ching-Shwun Lin a , Tom F. Lue a a Department of Urology, University of California, San Francisco, CA, USA b King Abdul Aziz University, Jeddah, Saudi Arabia abstract article info Article history: Accepted 8 November 2014 Available online xxxx Keywords: Erectile dysfunction Stem cell therapy Erectile Dysfunction (ED) is a common disease that typically affects older men. While oral type-5 phosphodieserase inhibitors (PDE5Is) represent a successful first-line therapy, many patients do not respond to this treatment leading researchers to look for alternative treatment modalities. Stem cell (SC) therapy is a promising new frontier for the treatment of those patients and many studies demonstrated its therapeutic effects. In this article, using a Medline database search of all relevant articles, we present a summary of the scientific principles behind SCs and their use for treatment of ED. We discuss specifically the different types of SCs used in ED, the methods of delivery tested, and the methods attempted to enhance SC therapy effect. In addition, we review the current preclinical literature on SC therapy for ED and present a summary of its findings in addition to the single clinical trial published. © 2014 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1.1. ED . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1.2. Mechanism of erection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1.3. Aging and ED . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1.4. Metabolic syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1.5. Prostate cancer therapy-related ED . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1.6. Peyronie's disease (PD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2. Types of stem cells used in ED . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.1. ESC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.2. Endothelial progenitor stem cells (EPSCs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.3. Bone marrow-derived stem cell (BMSC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.4. Skeletal muscle-derived stem cell (SKMSC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.5. Neural crest SCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.6. Adipose tissue-derived stem cell (ADSC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.7. Testis SC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.8. Human urine SC (USC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3. Methods of SC delivery for ED treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4. Methods to enhance the therapeutic effects of SCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 5. Assessment of outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 6. Clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 7. Immunocompatibilty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 8. Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Advanced Drug Delivery Reviews xxx (2014) xxx–xxx ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on “Regenerative Medicine Strategies in Urology” ☆☆ Author disclosure statement: No competing financial interests exist. ⁎ Corresponding author at: University of California, San Francisco, Box 0738, 1600 Divisadero St., MZ Bldg A, Room A609, San Francisco, CA 94143, USA. Tel.: +1 415 885 7748; fax: +1 415 885 7443. E-mail address: amjadwal@yahoo.com (A. Alwaal). ADR-12708; No of Pages 8 http://dx.doi.org/10.1016/j.addr.2014.11.012 0169-409X/© 2014 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr Please cite this article as: A. Alwaal, et al., Stem cell treatment of erectile dysfunction, Adv. Drug Deliv. Rev. (2014), http://dx.doi.org/10.1016/ j.addr.2014.11.012