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Stem Cell Activation in the Major Pelvic Ganglion is enhanced by Stromal Derived Factor-1 Penile Injections following Nerve Injury

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Sources of Funding: None

Introduction

Stem cells are believed to play a role in nerve regeneration following nerve injury. Stromal Derived Factor-1 (SDF1) is potent stem cell chemokine. We investigated whether penile injections with SDF1 following bilateral nerve crush injury (BCNI) can enhance stem cell recruitment and activation in the major pelvic ganglion (MPG).

Methods

Sprague Dawley (350g) male rats underwent sham procedure or BCNI (n=10/group). Starting on the day of surgery, BCNI animals received penile injections with 1ug of SDF1 or saline QOD for 5 injections. Sham animals received saline penile injections only. 2 weeks after BCNI, intracorporeal pressure (ICP) response to cavernous nerve stimulation was assessed (n=5/group) and MPGs were collected and RNA was isolated (n=5/group). Stem cell activity in the MPG was assessed using a stem cell expression array expressed as mean fold-change ± SE normalized to sham.

Results

SDF1 penile injections resulted in improved ICP preservation following BCNI compared to animals receiving saline injections. Sham animals had significantly greater (P<0.05, 1-way ANOVA with Tukey’s post-hoc testing) than BCNI+saline at all voltages (2, 4, 6, 8v), whereas there was no significant difference between Sham and BCNI+SDF1 at any voltages. Additionally, BCNI+SDF1 had greater ICP at 2v and 4v compared to BCNI+saline (0.40±0.09 vs. 0.11±0.08, p<0.05 and 0.47±0.11 vs. 0.12±0.08, p<0.05, respectively). Stem cell-associated gene expression normalized to Shams was globally increased following BCNI and BCNI+SDF1 had a greater increase in expression compared to BCNI+saline (7.89±0.67 fold vs. 1.87±0.15 fold, p<0.0001). On subset analysis, stem cell pathways had significantly greater expression in BCNI+SDF1 compared to BCNI+saline including cytokines and growth factors (6.45±0.63 vs. 1.86±0.13, p<0.0001), Notch pathway (7.72±0.96 vs. 1.95±0.17, p<0.0001), Wnt pathway (7.01±0.68 vs. 1.87±0.12, p<0.0001), mesenchymal stem cell markers (6.33±1.16 vs. 1.82±0.40, p=0.0015), and neural cell lineage markers (6.63±0.51 vs. 1.85±0.14, p=0.0003).

Conclusions

SDF1 penile injections improve preservation of erectile function following BCNI and are associated with increased stem cell pathway activation in MPG.

Funding

None

Authors
Nikolai Sopko
Hotaka Matsui
Takahiro Yoshida
Xiaopu Liu
Max Kates
Trinity Bivalacqua
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