Mesenchymal stem cell therapy for the treatment of erectile dysfunction.

E rectile dysfunction (ED) is defined as the consistent inability to achieve or maintain an erection sufficient for satisfactory sexual relations. ED is a common global problem affecting an estimated 150 million men worldwide, and it is estimated that by the year 2025, 322 million men will be affected by this disease [1]. However, there are many limitations with the current medications available for the treatment of ED. A study by Carvalheira et al. found that of those patients who were prescribed a phosphodiesterase type 5 inhibitors (PDE5), only 45% were still using the medication over the 3-year follow-up period [2]. Of the patients that discontinued the PDE5, 38% reported the reason to be ineffectiveness of the drug. Over the past decade, there has been growing interest in the use of stem cells to treat ED. Stem cells are by definition capable of selfrenewal and differentiation into one or several more terminally differentiated phenotypes. Furthermore, (mesenchymal) stem cells (MSC) have been described as site-regulated “drugstores” in vivo as a result of the discovery of their potent trophic and immunomodulatory activities [3]. Unlike conventional treatments currently used for the treatment of ED, these properties render stem cell therapy an excellent candidate to offer a potent treatment and potentially a cure for the ED patient. Contemporarily, a major concern regarding stem cell therapy for ED is the inappropriate claim made by centers regarding the efficacy of stem cells for ED patients. The majority of the research conducted with stem cells for this indication has been in the preclinical investigational phase, and thus represents level 5 evidence at best. There has been only one published clinical trial with seven patients with diabetes suggesting some transient short-term benefits with umbilical cord stem cells to treat ED [4]. Despite the lack of clinical data, there are numerous centers throughout the world offering patients stem cells to treat this condition, charging cash for this treatment and in many cases not even offering true stem cells. The International Society for Cellular Therapy (ISCT) has recommended minimum criteria for defining multipotent human mesenchymal stem stromal cells. These cells must express CD105, CD73, and CD90, and they must lack expression of CD34, CD45, CD14, CD11b, CD79-α, CD19, and HLA-DR surface molecules. MSC must also differentiate into osteoblasts, chondroblasts, and adipocytes ex vivo. The concern is that many of the centers offering stem cell therapy for ED do not follow the recommended criteria set out by the ISCT, and these centers are not being monitored for what type of cells are actually being injected. The first stem cell study for the treatment of ED was published in 2004. This study was the only study to use embryonic stem cells to treat ED. There have up until now been a total of 34 published preclinical studies assessing stem cell therapy for ED. Of these studies, 19 have focused on cavernous nerve injury (CNI) and 10 focused on diabetes mellitus (DM). The majority of these studies have employed adipose-derived stem cells, and transplantation of the stem cells has mainly been performed via intracavernous injection. Some studies have attempted alternative strategies such as peri-prostatic application (either or not linked to a scaffold) and intravenous injection. 1105