Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous

Akio Takayanagi MD; Masanori Sasaki MD, PhD; Yuko Kataoka-Sasaki MD, PhD; Ko Kobayashi MD, PhD; Yohei Matsuda MD; Shinichi Oka MD, PhD; Naoya Masumori MD, PhD; Jeffery D. Kocsis PhD; and Osamu Honmou MD, PhD

ONLINE: July 24, 2015 – The Journal of Sexual Medicine

DOI: 10.1111/jsm.12957


Introduction

Erectile dysfunction (ED) after radical prostatectomy (RP) is a common problem for men with low and intermediate risk localized prostate cancer. Damage to the cavernous nerve (CN) during a nerve-sparing RP is thought to be the major contributing cause in most cases.

Treatments such as phosphodiesterase type 5 inhibitors and penile rehabilitation can help, but have varying rates of success.

Mesenchymal stem cells (MSCs) come from adult bone marrow. They are thought to secrete neurotrophic factors, cytokines, and anti-inflammatory molecules that can protect and regenerate nerves and modify the immune response.  

This study investigated whether intravenously delivered MSCs could reduce postoperative ED in rats if administered before CN injury.

Materials and Methods

Male Sprague-Dawley rats were randomized into two groups. One group was assigned to receive MSCs intravenously. The other group received a sham treatment. The rats’ cavernous nerves were crushed immediately afterward.

Erectile function was evaluated by measuring intracavernous pressure (IP) and arterial pressure (AP). These measurements were taken before injury, one hour following injury, and then two weeks later.

Additional studies were performed to assess the health of the major nerve center, the major pelvic ganglion. 

Results

One hour after injury, erectile function (ICP/AP and ICP-AUC) was significantly decreased in both groups.

After two weeks, measures of erectile function (ICP/AP and ICP-AUC) in the MSC group were 41.3%, and 53.7% higher, respectively, than those of the control group.

“The MSC-preloaded group displayed less ED shortly after CN injury (Figure 2) and erectile function evaluated with physiologic analyses reached near normal values over the time course of two weeks,” the authors wrote.

“Collectively, these results indicate that the intravenous preload of MSCs prevented or reduced ED after RP,” they added.

Nerve preservation was also improved, with 58% more neurons preserved in the MSC group versus controls. 

Discussion

Rats who were intravenously preloaded with MSCs had “significant preservation” of erectile function. The fact that RP can be planned, administering MSCs before surgery may be practical and therapeutic.

Post-operative ED was found in both groups of rats. Those who had been infused with MSCs had less severe ED after CN injury and showed significant improvement at the two-week mark. It’s possible that the MSCs provided neuroprotection. MSCs also tended to home in on damaged lesion sites for greater therapeutic effectiveness.

“Given that intravenous infusion of MSCs derived from bone marrow has been used in a number of clinical studies with demonstrated safety, the prospect of using MSCs as an adjunct therapy for damaged nerve repairs should be considered,” they wrote.