title: Restoration of erectile function with intracavernous injections of endothelial progenitor cells after bilateral cavernous nerve injury in rats.
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.
authors: Division of Urology, Department of Surgery, Cathay General Hospital, New Taipei City, Taiwan.|School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.|PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: C H
authors: CH
authors: Liao
authors: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.|PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Y N
authors: YN
authors: Wu
authors: Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Y H
authors: YH
authors: Lin
authors: PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: R F
authors: RF
authors: Syu Huang
authors: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors: S P
authors: SP
authors: Liu
authors: Division of Urology, Department of Surgery, Cathay General Hospital, New Taipei City, Taiwan.|School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.|PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.|Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: H S
authors: HS
authors: Chiang
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000637:transplantation*; D007172:Erectile Dysfunction / Q000628:therapy*; D007382:Intermediate Filaments / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000294:innervation / Q000601:surgery; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014841:von Willebrand Factor / Q000096:biosynthesis
chemical_list: D014841:von Willebrand Factor; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat
keywords: bilateral cavernous nerve; endothelial progenitor cells; erectile dysfunction