Engineered cells shown to restore penile function

August 15, 2007

In the area of sexual dysfunction, tomorrow arrived a little earlier than many attendees of the AUA annual meeting may have anticipated.

The study is one of three selected by John J. Mulcahy, MD, PhD, clinical professor of urology (surgery) at the University of Arizona, Phoenix, as studies he feels his colleagues should note and remember.

Endothelial progenitor cells grown from autologous peripheral blood can be isolated, grown, and expanded to achieve mature endothelial cells. These cells are then injected back into diabetic animals with corporal damage to restore normal erectile function.

The authors of this study, from Wake Forest University, Winston-Salem, NC, noted that between 35% and 75% of men with diabetes present with ED. It is thought that the disease leads to impairment of endothelial cells. These cells lose the ability to release nitric oxide, subsequently reducing arterial inflow into corporal tissues of the penis.

Endothelial progenitor cells were isolated from the peripheral blood of donor rats, grown, expanded, and induced to grow into endothelial cell lineages. The cells were labeled with fluorescent dye and injected into the corpora of the diabetic rats. The animals showed significant im-provements in erectile function, and histologic examination showed that the labeled cells had survived and had been integrated into the corporal tissue of the rats.

The therapy might ultimately resolve a range of erectile dysfunction associated with disease processes outside of diabetes, according to Dr. Mulcahy. Aging is one of these. He cautioned that clinicians should not hope for a panacea because ED is often a multifactorial disease.

Prostatectomy for prostate cancer does not prohibit the use of subsequent testosterone replacement therapy.

Dr. Mulcahy cited a study from the Baylor College of Medicine, Houston, in which testosterone replacement therapy (TRT) was successfully administered to hypogonadal men who had undergone prostatectomy for prostate cancer.

"There was a time not so long ago when giving testosterone to men who had experienced prostate cancer would have been unthinkable. Many would have said it would be grounds for malpractice," said Dr. Mulcahy.

This thinking began to change after it was shown that PSA was a reliable marker for prostatic cellular activity, and studies of intermittent androgen ablation showed that many men could live well with both prostate cancer and normal testosterone levels, he explained.

In the Baylor study, symptomatic hypogonadal men with negative margins following prostatectomy and undetectable PSA were started on TRT. Twenty-one men, ages 51 to 80 years, began the therapy an average of 54.4 months following their prostatectomy. Average testosterone levels rose from 275.8 ± 124.9 ng/dL to 440.1 ± 294.6 ng/dL.

Nine of the 11 men contacted at the close of the study had scored positive on the Androgen Deficiency in Aging Males questionnaire before TRT. Only one of these scored positive at the close of the study. The investigators concluded that TRT was safe and effective at im-proving symptoms of hypogonadism following prostatectomy.

The symptoms of hypogonadism can have a severe impact on the quality of life, and the Baylor study shows that they need not be accepted, Dr. Mulcahy said.

"The key is careful and compulsive monitoring of PSA levels," he pointed out.

He noted that one of the issues not resolved by the study was when to initiate the therapy, and that it may not be necessary to wait for 4 to 5 years.

Less than two-thirds of robotic radical prostatectomy web sites give information related to postoperative erectile function. Many claim that the robotic procedure fares better in this outcome than open surgery does, despite the absence of any support of this claim.

"There is absolutely no reliable data showing that robotic prostatectomies produce better or worse outcomes than other procedures," Dr. Mulcahy said. "None whatsoever."

The current study, from Weill Medical College of Cornell University, New York, reviewed 75 institutional web sites and found that 39% had no sexual health function information at all, and that 42% copied information directly from the robot manufacturer's web site. Of the web sites that offered information about erectile function, 78% said that robotic procedures produced better sexual outcomes than open procedures did; 52% said that robotic procedures were better at preserving erectile function; and 26% stated that sexual recovery was faster with robotic procedures. Only seven of the 75 sites offered specific data to support their information, and only two of these provided data from their own institution.

"The whole area of incontinence and erectile function following prostatectomy is cloudy," Dr. Mulcahy said, adding that he felt that the recovery of sexual function following robotic and many other procedures was far longer and far lower than was being claimed by individuals and institutions alike.