Injections of Adipose Tissue-Derived Stem Cells and Stem Cell Lysate Improve Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury

Abstract

Introduction Erectile dysfunction (ED) remains a major complication after radical prostatectomy. The use of adipose tissue-derived stem cells (ADSC) has shown promising results for the treatment of ED. However, the mechanisms of action for stem cell therapy remain controversial, with increasing evidence pointing to paracrine pathways. Aim To determine the effects and to identify the mechanism of action of ADSC and ADSC-derived lysate in a rat model of cavernous nerve (CN) crush injury. Methods Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: one group underwent sham operation, while three groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of ADSC, lysate, or vehicle only (injured controls). Erectile function was assessed by cavernous nerve electrostimulation at 4 weeks. Penile tissue was collected for histology. Main Outcome Measures Intracavernous pressure increase upon CN stimulation; neuronal nitric oxide synthase (nNOS) content in the dorsal penile nerve; smooth muscle content, collagen content, and number of apoptotic cells in the corpus cavernosum. Results Both ADSC and lysate treatments resulted in significant recovery of erectile function, as compared to vehicle treatment. nNOS content was preserved in both the ADSC and lysate group, with significantly higher expression compared to vehicle-treated animals. There was significantly less fibrosis and a significant preservation of smooth muscle content in the ADSC and lysate groups compared to injured controls. The observed functional improvement after lysate injection supports the hypothesis that ADSC act through release of intracellular preformed substances or by active secretion of certain biomolecules. The underlying mechanism of recovery appears to involve neuron preservation and cytoprotection by inhibition of apoptosis. Conclusions Penile injection of both ADSC and ADSC-derived lysate can improve recovery of erectile function in a rat model of neurogenic erectile dysfunction.

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.…”

Potential application of adipose tissue-derived stem cells for urological Disease

“…Similar tests conducted by Das et al [88] and Ryu et al [89] in models of diabetic ED additionally found improved erectile function and recovery of pathological changes in SVF treated groups. Our previous work also illustrated the beneficial effect of immediate and delayed intracavernous injection of uncultured autologous SVF, penile injection of ADSCs or ADSC derived lysate in CNI model [90,91]. We also proved the beneficial effect of ADSCs on radiation induced ED model, hyperlipidemia induced ED model, and type 2 diabetes induced ED model [92][93][94].…”

Stem cells: novel players in the treatment of erectile dysfunction

“…126 Third, ADSCs and cell-free lysates derived from ADSCs were injected into the penis in a rat model of cavernous nerve injury, resulting in a significant recovery of erectile function in both treatments compared with the control group. 127 In the treated rats, nNOS and smooth muscle content were preserved, and less fibrosis occurred in the corpus cavernosum. The underlying mechanisms involved neuron preservation and cytoprotection by inhibition of apoptosis by releasing intracellular preformed substances or by active secretion of certain biomolecules.…”