Stem cell, low-energy shock wave and phosphodiesterase type 5 inhibitor therapy to promote erectile function recovery in a rat pelvic neurovascular trauma model

Abstract

Abstract Introduction Battlefield pelvic injuries can have long-lasting debilitating effects, including erectile dysfunction (ED) in young soldiers. We investigated whether phosphodiesterase-5 inhibitor (PDE5i), low-energy shock wave (LESWT) and/or mesenchymal stem cell (MSC) therapy could improve erectile function (EF) after pelvic injury. Methods Lewis rats 10–12 weeks old were used. We had nine experimental groups (n=6/group): Sham, Injury alone, PDE5i, LESWT, MSC, LESWT+PDE5i, LESWT+MSC, MSC+PDE5i, and LESWT+PDE5i+MSC. Pelvic injury was created by performing bilateral cavernous nerve crush injury and internal pudendal bundle ligation. Bone marrow-derived MSCs (CD29+, CD90+, CD34−, CD31−) were injected (2×106 cells) into the corpora cavernosum. Rats received LESWT (1000 pulses at 0.06 mJ/mm2 and 3Hz) three times per week or sildenafil (PDE5i) in drinking water at ~10 mg/kg/day for four weeks. At 6thweek intracavernous pressure (ICP; mmHg) was recorded as EF outcome measure. Results Erectile function was significantly (P<0.001) improved with PDE5i+LESWT therapy (max ICP 131±16, average ICP 116±11, change ICP 63±13) compared to untreated injury control (max ICP 88±24, average ICP 81±13, change ICP 16±23); ICPs became nearly normal, similar to uninjured sham group. LESWT alone improved (P<0.05) EF (max ICP 105±14; change in ICP 39±15) compared to untreated injury control. Also, MSC alone improved (p<0.05) EF compared to injury control. In both LESWT and MSC alone therapies EF recovery was partial. The other combination therapies and PDE5i alone did not show significant (P>0.05) EF recovery. Conclusion LESWT, MSC and/or PDE5i combination therapy appears to be highly promising in EF recovery.