The Effect of Intracavernous Injection of Adipose Tissue-Derived Stem Cells on Hyperlipidemia-Associated Erectile Dysfunction in a Rat Model

Abstract

Introduction Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors. Aim To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED. Methods Twenty-eight male rats were induced to develop hyperlipidemia with a high fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for one week, labeled with 5-ethynyl-2′-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate-buffered saline (PBS). At 3 and 14 days post-transplantation, 4 rats in the HR+ADSC group were sacrificed for tracking of the transplanted cells. At one month post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function and penile histology. Main Outcome Measures Erectile function was assessed by intracavernous pressure measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry. Results Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean intracavernous pressure/mean arterial pressure ratio was significantly lower in HR+PBS than in NR+PBS or HR+ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR+PBS than in HR+ADSC. Smooth muscle content was significantly higher in both HR groups than in NR. Conclusions Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED.

Isolation and passage of muscle-derived stem cells from the rat penile corpora cavernosa and induction of differentiation into smooth muscle cells

“…Some studies confirmed that embryonic stem cells can be used for the treatment of neurogenic ED (Eglitis and Mezey 1997). Studies of the effect of mesenchymal (Bivalacqua et al 2007;Qiu et al 2012), human neural crest (Song et al 2008), and adipose tissue-derived stem cells (Albersen et al 2010;Garcia et al 2010;Huang et al 2010) on ED treatment have also been performed by other researchers using intracavernous injection of these cells in rats. The results indicated that ED could be improved to a certain extent when treated with these cells.…”

Stem cells: novel players in the treatment of erectile dysfunction

“…First, ADSCs were injected into the penis to examine their effects on a rat model of hyperlipidemiaassociated ED; elevated erectile function was demonstrated after ADSCs transplantation. 124 An increase in neuronal nitric oxide synthase (nNOS)-positive nerve fibres and ECs was observed in the experimental group compared to the control animals. The authors indicated that the underlying mechanisms involved cytokine and growth factor secretion rather than stem cell differentiation.…”

“…Investigation of the long-term fate of ADSCs is required before human trials could be considered, although the lack of ADSCs in tissue sections observed for a 28-day follow-up period implies that the potential of these cells to persist and undergo malignant transformation is limited. 124 Second, Garcia and co-workers 125 observed improved erectile function in type-2 diabetic rats after autologous ADSC injection. This observation was based on decreased numbers of apoptotic cells in the corpus cavernosum, increased numbers of sinusoid ECs and increased expression of nNOS in the penile nerves.…”

Aspects of Urological Tissue Engineering

“…Increased levels of nitric oxide synthase and alpha smooth muscle actin were also observed. (Huang, 2010) This study provides preliminary evidence that adipose derived mesenchymal stem cells can be used to ameliorate the urologic complications that arise in urologic settings. In order to obtain continual exposure of these factors in the afflicted areas, seeding these cells upon implantable nanofabricated materials may allow for immediate regeneration accompanied by long term maintenance.…”

“…Dyslipidemia has been associated with a variety of poorly compliant physiological conditions including erectile dysfunction. (Huang, 2010) Damage occurs to the cavernous endothelium and associated nerves through mechanisms that are not quite fully understood. In order to facilitate recovery, adipose derived mesenchymal stem cells have been utilized to augment repair in the penis with the understanding that various factors secreted from mesenchymal stem cells promote re-growth of endothelium and improved nerve conduction.…”