Intracavernous administration of bone marrow mononuclear cells: a new method of treating erectile dysfunction?
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Intracavernous administration of bone marrow mononuclear cells: a new method of treating erectile dysfunction? Thomas E Ichim1*, Timothy Warbington2, Octav Cristea3, Joseph L Chin3 and Amit N Patel4
Abstract While PDE5 inhibitors have revolutionized treatment of ED, approximately 30% of patients are non-responsive. A significant cause of this is vascular and smooth muscle dysfunction, as well as nerve atrophy. Autologous administration of bone marrow mononuclear cells (BMMC) has been performed in over 2000 cardiac patients without adverse effects, for stimulation of angiogenesis/regeneration. Despite its ease of access, and dependence on effective vasculature for function, comparatively little has been perform in terms of BMMC therapy for ED. Here we outline the rationale for use of autologous BMMC in patients with ED, as well as provide early safety data on the first use of this procedure clinically.
Introduction Erectile responses require a coordinated increase in arterial inflow, which originates from the pudendal arteries, relaxation of the corporal smooth muscle, and inhibition of venous outflow [1,2]. Key to this response is production of nitric oxide (NO) from endothelial cells and nonadrenergic noncholinergic (NANC) postganglionic parasympathetic neurons, as well as responsiveness to this. NO binds to, and activates, the enzyme guanylate cyclase, which in turn catalyzes the generation of cGMP from GTP. As a result, cGMP induces a cascade of signals in the smooth muscle cells resulting in relaxation [3]. Breakdown of cGMP in the cavernosal tissue is mediated by PDE-5. Increasing the duration of NO signaling by preventing cGMP breakdown is the main mechanism of action for the successful PDE-5 inhibitor class of drugs which currently are used as first-line treatment of ED [4]. Interestingly, recent studies have shown that these drugs have other beneficial effects such as stimulation of bone marrow endothelial progenitor cell function [5-9], inhibition of smooth muscle cell apoptosis [10,11], preservation/restoration of function in post-prostatectomy settings [12,13] and activation of mesolimbic dopaminergic neurons in the CNS to promote sexual behavior [14]. * Correspondence: [email protected] 1 Institute for Molecular Medicine, Huntington Beach, CA, USA Full list of author information is available at the end of the article
Unfortunately, a significant number of patients are resistant to effects of PDE5 inhibitors [15]. Major factors associated with this include atherosclerosis, nerve damage and smooth muscle atrophy [16]. Several approaches have demonstrated some promise in the improvement of responsiveness to PDE5 inhibitors including propionyl-Lcarnitine [17,18], intracavernous PGE1 [19], and testosterone gel [20,21]. However these studies are early and do not address the underlying biological cause in many of the situations of ED. Since the majority of ED cases appear to be a manifestation of systemic atherosclerotic disease [22,23], and various forms of stem cell therapy have
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