Restoration of erectile function with intracavernous injections of endothelial progenitor cells after bilateral cavernous nerve injury in rats
Journal
Andrology
Journal Volume
3
Journal Issue
5
Pages
924-932
Date Issued
2015
Author(s)
Abstract
Endothelial 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; ΔICP/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. ? 2015 American Society of Andrology and European Academy of Andrology.
Subjects
Bilateral cavernous nerve; Endothelial progenitor cells; Erectile dysfunction
SDGs
Other Subjects
endothelial nitric oxide synthase; neurofilament 1 protein; neurofilament protein; neuronal nitric oxide synthase; unclassified drug; von Willebrand factor; endothelial nitric oxide synthase; neuronal nitric oxide synthase; Nos1 protein, rat; Nos3 protein, rat; von Willebrand factor; animal experiment; animal model; animal tissue; Article; cavernous nerve injury; controlled study; corpus cavernosum; endothelial progenitor cell; erectile dysfunction; immunofluorescence; male; mean arterial pressure; nerve injury; nonhuman; penis injury; priority journal; rat; rat model; smooth muscle fiber; Sprague Dawley rat; animal; arterial pressure; biological therapy; biosynthesis; cell culture; cytology; disease model; drug effects; endothelial progenitor cell; erectile dysfunction; innervation; intermediate filament; metabolism; penis; penis erection; procedures; randomization; smooth muscle cell; surgery; transplantation; Animals; Arterial Pressure; Cell- and Tissue-Based Therapy; Cells, Cultured; Disease Models, Animal; Endothelial Progenitor Cells; Erectile Dysfunction; Intermediate Filaments; Male; Myocytes, Smooth Muscle; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Penile Erection; Penis; Random Allocation; Rats; Rats, Sprague-Dawley; von Willebrand Factor
Publisher
Blackwell Publishing Ltd
Type
journal article