Advances In Stem Cell Therapy for Peyronie’s Disease

What is Peyronie’s Disease? 

Peyronie’s disease (PD) is an uncommon condition involving middle-aged men. It is caused by an inflammation in the tunica followed by scarring and penile curvature. It is considered a fibrotic disorder of the penis that is characterized by the formation of collagen plaques on the tunica albuginea that may cause penile curvature, narrowing and shortening that subsequently lead to erectile dysfunction (ED).

Penises vary in shape and size, and having a curved erection isn’t necessarily a cause for concern. But Peyronie’s disease causes a significant bend or pain in some men. This can prevent the patient from having sex or might make it difficult to get or maintain an erection. For many men, Peyronie’s disease also causes stress and anxiety. Penile shortening is another common concern. 

The condition rarely goes away on its own. In most cases the condition will remain as is or worsen. Early treatment soon after developing the condition may keep it from getting worse or even improve symptoms. 

Patients with PD present early after the onset of the disease (within 6 months) with penile pain and curvature upon erection. PD is characterized by a palpable plaque in the tunica albuginea and is usually associated with ED. 

How Common is PD? 

The prevalence of PD varies because it is usually underreported by men. Schwarzer et al. conducted a large survey involving 8,000 men and noted a prevalence of 3.2%. DiBenedetti et al. reported a prevalence of 13% among males ages 18 years and older; this figure includes men diagnosed with, treated for, or who recently reported penile symptoms of PD.

It occurs in middle aged men, most of whom are between 40 and 59 years. 

What Causes PD? 

One of the theories helping to explain the pathophysiology of PD is microvascular trauma. This results in edema, inflammation, and fibrin deposition within the tunica albuginea. During the acute phase of PD, transforming growth factor (TGF)-β1 is overexpressed, and this induces fibroblasts to increase collagen synthesis. TGF-β1 can induce its own synthesis and contributes to continuous fibrotic changes.

PD is associated with Dupuytren’s contracture and certain human leukocyte antigen subtypes. An autoimmune theory of the pathophysiology of PD was proposed since serology of patients with PD has detected high titers of anti-elastin antibodies. 

How is Diagnosed? 

Penile curvature is the first symptom  of the disease and develops in 94% of patients. ED is usually present in patients with PD, developing in 30-50% of those patients. 

It is clinically diagnosed based on detailed history and penile examination. Measurement of penile curvature and palpation of plaque are important elements of this examination. There are 2 phases of PD, acute and chronic. 

The acute phase or inflammatory phase is characterized by penile pain in a flaccid or erect state and palpable plaque; it typically lasts for 12-18 months after onset. In the chronic phase the pain disappears and penile curvature stabilizes. 

What are The Treatment Options? 

In general, medical treatment is often used during the acute phase of the disease whereas surgery is used during the stable phase. Non surgical treatment includes oral or intralesional drugs. Oral therapies include vitamin E and paraaminobenzoate, colchicine,  and tamoxifen. 

Intralesional injection therapy includes injection with interferon-alpha-2b, verapamil and collagenase. Surgery is reserved for patients who do not respond to medical therapy or for men with severe penile curvature that affects sexual intercourse. Surgical procedures are either penile shortening or penile lengthening to correct the curvature.

Regenerative medicine is a novel therapy for the treatment of PD using mesenchymal stem cells with both curative and preventive potential. 

Use of Mesenchymal Stem Cells for PD Treatment 

Stem cells are self-renewing cells with a high degree of plasticity that can differentiate into multiple cell lines; they can be used to repair genetically damaged tissue or altered organs. 

Many studies have described the use of stem cells to treat urologic conditions such as PD, incontinence, infertility, and ED.

Adipose derived stem cells (ADSC) and other mesenchymal stem cells, such as umbilical cord derived MSCs have immunomodulatory properties, they are easy to isolate and lack histocompatibility complex II expression and their immunosuppressive action is mediated by prostaglandin E2. 

Studies Corroborating Their Use

In 2013, the first study used ADSCs to treat PD in an animal model. TGF-β1 was used to induce fibrosis within the tunica albuginea of rats. A day after injection of TGF-β1, human ADSCs were administered. Erectile function significantly improved after the therapy. This is the first study using xenogeneic cells that were transplanted into immunocompetent animals without the use of immunosuppressant drugs. The results were promising. 

Another study evaluated the role of ADSC injection in the chronic phase of PD in a rat model. Rats were injected with human ADSCs 1 month after injection of TGF-β1 (mimicking the chronic phase of PD) and they displayed less fibrosis, decreased expression of collagen III and decreased expression of several fibrosis related genes. The same study also found that fibrotic plaques tended to partially regress spontaneously after 60 days.

The first study using placental matrix-derived mesenchymal stem cells (PM-MSC) to manage PD in humans involved a small sample of 5 subjects. Patients with PD with a palpable plaque received intracavernous injections of PM-MSC. Penile curvature improved significantly 6 weeks, 3 months, and 6 months after injection. Seven of the 10 plaques initially evident on ultrasonography disappeared completely at 3 months.

Conclusions and Therapy at Zignagenix 

Different studies have demonstrated that stem cell therapy is effective for the treatment of PD in humans and animals. Even though the human studies have only involved small samples, the results have been great on all of them.

At our clinic we perform a combined therapy using umbilical cord mesenchymal stem cells. The therapy includes intravenously (IV) infused stem cells with exosomes, and a localized injection in the affected area, that can help improve decreasing the fibrotic tissue that is causing the penile curvature, while also improving the erectile function, that can be affected in this condition. 

Source: 

Moussa M, Abou Chakra M, Moussa Y. Advances in stem cell therapy for the treatment of Peyronie’s disease. Intractable Rare Dis Res. 2020;9(1):10-13. doi:10.5582/irdr.2019.01130

https://www.mayoclinic.org/diseases-conditions/peyronies-disease/symptoms-causes/syc-20353468

Images from: https://theriwave.com/peyronies-disease/