title: Recruitment of intracavernously injected adipose-derived stem cells to the major pelvic ganglion improves erectile function in a rat model of cavernous nerve injury.
abstract: BACKGROUND
  Intracavernous (IC) injection of stem cells has been shown to ameliorate cavernous-nerve (CN) injury-induced erectile dysfunction (ED). However, the mechanisms of action of adipose-derived stem cells (ADSC) remain unclear.
  
  
  OBJECTIVE
  To investigate the mechanism of action and fate of IC injected ADSC in a rat model of CN crush injury.
  
  
  METHODS
  Sprague-Dawley rats (n=110) were randomly divided into five groups. Thirty-five rats underwent sham surgery and IC injection of ADSC (n=25) or vehicle (n=10). Another 75 rats underwent bilateral CN crush injury and were treated with vehicle or ADSC injected either IC or in the dorsal penile perineural space. At 1, 3, 7 (n=5), and 28 d (n=10) postsurgery, penile tissues and major pelvic ganglia (MPG) were harvested for histology. ADSC were labeled with 5-ethynyl-2-deoxyuridine (EdU) before treatment. Rats in the 28-d groups were examined for erectile function prior to tissue harvest.
  
  
  METHODS
  IC pressure recording on CN electrostimulation, immunohistochemistry of the penis and the MPG, and number of EdU-positive (EdU+) cells in the injection site and the MPG.
  
  
  CONCLUSIONS
  IC, but not perineural, injection of ADSC resulted in significantly improved erectile function. Significantly more EdU+ ADSC appeared in the MPG of animals with CN injury and IC injection of ADSC compared with those injected perineurally and those in the sham group. One day after crush injury, stromal cell-derived factor-1 (SDF-1) was upregulated in the MPG, providing an incentive for ADSC recruitment toward the MPG. Neuroregeneration was observed in the group that underwent IC injection of ADSC, and IC ADSC treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum.
  
  
  CONCLUSIONS
  CN injury upregulates SDF-1 expression in the MPG and thereby attracts intracavernously injected ADSC. At the MPG, ADSC exert neuroregenerative effects on the cell bodies of injured nerves, resulting in enhanced erectile response.
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Fandel
authors.forename: Maarten
authors.initials: M
authors.lastname: Albersen
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Qiu
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Ning
authors.forename: Lia
authors.initials: L
authors.lastname: Banie
authors.forename: Tom F
authors.initials: TF
authors.lastname: Lue
authors.forename: Ching-Shwun
authors.initials: CS
authors.lastname: Lin
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005724:Ganglia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007001:Hypogastric Plexus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection; D010413:Penis / Q000294:innervation*; D011468:Prostatectomy / Q000009:adverse effects*; D060525:Pudendal Nerve / Q000293:injuries* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013997:Time Factors
chemical_list: D054377:Chemokine CXCL12; D003094:Collagen; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat