Stem cell therapy for erectile dysfunction

Abstract

Erectile dysfunction (ED) is an important health problem that has commonly been clinically treated using phosphodiesterase type 5 inhibitors (PDE5Is). However, PDE5Is are less effective when the structure of the cavernous body has been severely injured, and thus regeneration is required. Stem cell therapy has been investigated as a possible means for regenerating the injured cavernous body. Stem cells are classified into embryonic stem cells and adult stem cells (ASCs), and the intracavernous injection of ASCs has been explored as a therapy in animal ED models. Bone marrow-derived mesenchymal stem cells and adipose tissue-derived stem cells are major sources of ASCs used for the treatment of ED, and accumulated evidence now suggests that ASCs are useful in the restoration of erectile function and the regeneration of the cavernous body. However, the mechanisms by which ASCs recover erectile function remain controversial. Some studies indicated that ASCs were differentiated into the vascular endothelial cells, vascular smooth muscle cells, and nerve cells that originally resided in the cavernous body, whereas other studies have suggested that ASCs improved erectile function via the secretion of anti-apoptotic and/or proangiogenic cytokines rather than differentiation into other cell types. In this paper, we reviewed the characteristics of stem cells used for the treatment of ED, and the possible mechanisms by which these cells exert their effects. We also discussed the problems to be solved before implementation in the clinical setting.

Keywords: Erectile dysfunction, Stem cell therapy, Bone marrow-derived mesenchymal stem cells, Adipose tissue-derived stem cells, Endothelial progenitor cells, Adrenomedullin, Angiopoietin-1

Core tip: Adult stem cells (ASCs) have been used for the treatment of erectile dysfunction. Although previous studies reported that ASCs differentiated into cells that originally resided in the cavernous body, recent studies indicate that the major, if not all, effects of ASCs on erectile function are achieved through the secretion of paracrine factors rather than their direct differentiation into the cells in the cavernous body. Among various cytokines that ASCs produce, we have recently identified adrenomedullin as a candidate peptide that is implicated in the restoration of erectile function. We introduced these data in this review.