Restoration of erectile function with intracavernous injections of endothelial progenitor cells after bilateral cavernous nerve injury in rats

Abstract

SUMMARYEndothelial progenitor cells (EPCs) are bone marrow-derived endothelial cells capable of circulating, proliferating, and differentiating into mature endothelial cells. Circulating EPCs can be directly recruited to some extent at sites of injury, and their administration could accelerate repair or endothelialization of the damaged tissue. We investigated the effects of intracavernous injections of EPCs into the corpora cavernosa of rats with erectile dysfunction (ED) caused by bilateral cavernous nerve (CN) injury. Overall, 24 male Sprague-Dawley rats were randomized into three groups: sham surgery, vehicle-only, or EPC treatment. Rats in the EPC treatment and vehicle-only groups were subjected to bilateral CN injury before injection of EPCs or vehicle, respectively, into the corpora cavernosa. Four weeks after surgery, erectile function was assessed by measuring maximum intracavernosal pressure (ICP), change in ICP, area under the ICP curve, and ratio of change in ICP and mean arterial pressure (MAP; DICP/MAP). Penile tissue was histomorphometrically analyzed for the expression of neural nitric oxide synthase (nNOS), neurofilament-1 (NF-1), von Willebrand factor (vWF), endothelial NOS (eNOS), and smooth muscle cell content. Maximum ICP and all other functional parameters of erectile function were significantly reduced in the vehicle-only group vs. the sham and EPC treatment groups (all p < 0.001). Smooth muscle cell content was decreased in the vehicle-only vs. the sham and EPC treatment groups (both p < 0.01). Expressions of vWF and eNOS in the dorsal artery were significantly higher in the EPC treatment than the vehicle-only group (p < 0.05). In conclusion, EPC treatment restored erectile function in a rat model of bilateral CN injury through recruitment of EPCs toward the dorsal artery and preservation of smooth muscle cells in the corpus cavernosum. These findings elucidate the therapeutic potential of EPCs for treating ED in humans.

Smooth Muscle Progenitor Cells Preserve the Erectile Function by Reducing Corporal Smooth Muscle Cell Apoptosis after Bilateral Cavernous Nerve Crush Injury in Rats

“…We have also previously reported that EPC treatment restored EF in a rat model of bilateral CN injury through recruitment of EPCs toward the dorsal artery and preservation of corporal SMCs. These findings support the therapeutic potential of progenitor cells for treating ED in humans [14]. SPCs can limit plaque development and promote changes in plaque composition toward a stable phenotype in mice [15].…”

Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects

“…Regarding treatment strategies, a recent study showed that intracavernous injection of EPCs into the corpora cavernosa of rats with erectile dysfunction caused by bilateral cavernous nerve injury could restore erectile function [227]. In summary, the close correlation between erectile dysfunction and penile vascular dysfunction suggests that EPCs may have great therapeutic potential.…”

Maintenance of the contractile phenotype in corpus cavernosum smooth muscle cells by Myocardin gene therapy ameliorates erectile dysfunction in bilateral cavernous nerve injury rats

“…Penile erectile function was assessed using ICP and MAP tests as previously reported (Liao et al ., ). The CNs were exposed and a bipolar, stainless steel electrode was used for nerve stimulation.…”

“…Radical prostatectomy (RP) is the primary treatment for patients with localized prostate cancer. However, the incidence rate of erectile dysfunction (ED) post‐operation remains as high as 30–87% (Liao et al ., ). Currently, the pathophysiology of RP‐ED has not been well‐elucidated (Weyne et al ., ).…”