Stem Cell Treatment for Vascular Erectile Dysfunction: A Paradigm Shift

Erectile Dysfunction (ED) is the incapacity to obtain or maintain a penile erection sufficient for satisfactory sexual performance. The causative factors could be psychogenic or organic in nature. Psychogenic causes represent the psychological factors behind ED, whereas organic causes include vascular dysfunction, neurological disorders, hormonal imbalance, etc. Epidemiological surveys indicate that most young men (< 40years) suffer from psychogenic ED, while ED patients belonging to the higher age group (> 40years) predominantly have organic ED. The relationship issues and social expectations related to ED have serious implications for mental health. Several treatment interventions are present for this condition. However, their limited efficacy has prompted the search for an alternative.

Vasculogenic ED

ED caused by vascular dysfunction is named as Vasculogenic or vascular ED. It occurs due to changes in blood flow to penis arising from abnormalities in blood vessels. Most patients with organic ED have vascular origins. Depending on the underlying mechanisms, Vasculogenic ED is broadly classified as:

• Arteriogenic or Arterial ED: It describes the blockage in arteries that supply blood to penis. Cholesterol accumulates in vessels (atherosclerosis) and blocks them, which reduces blood flow.
• Venogenic or Venous ED: It is also referred to as venous leak syndrome. Blood flow from the arteries is adequate in the venous ED. However, blood from penis drains faster through veins making it challenging to maintain erection.

Causes of Vascular Erectile Dysfunction

The primary process behind erection is the relaxation of vascular smooth muscle cells surrounding the blood vessels of penis. The relaxed smooth muscles increase the vessel diameter and the resultant blood flow to penis. As this tissue fills, it compresses surrounding veins, reducing blood outflow and allowing the erection to become firm.  Disruptions in this process can lead to Erectile Dysfunction (ED). Therefore, ED is frequently associated with cardiovascular conditions. Common contributors to vascular ED include:

• Peripheral artery disease: It results from blockage in the arteries in the lower extremities.
• Coronary artery disease: It describes obstruction in the arteries of heart lowering circulation throughout the body including penis.
• High Blood Pressure: Chronic hypertension damages blood vessel walls, affecting their ability to expand properly.
• High Cholesterol: Promotes atherosclerosis, leading to reduced blood flow.
• Diabetes: Elevated glucose deposits in vessels, damaging them and impairing circulation.
• Aging: The comorbidities increase with age while tissue deteriorates, contributing to ED.

Vascular Erectile Dysfunction Symptoms

The cellular mechanisms behind vasculogenic ED are the release of nitric oxide by vessel cells. Under normal circumstances, sexual stimulation prompts the release of nitric oxide, which helps produce a molecule called cGMP. cGMP activates pathways that decrease the calcium influx in muscles and leads to their relaxation. The erection is maintained until penile phosphodiesterase degrades cGMP, causing muscle contraction and reversal of the entire process. ED occurs due to a disruption in the process, resulting in the following symptoms:

• Difficulty achieving an erection
• Problems maintaining an erection
• Reduced interest in sexual activity
• Performance-related anxiety

Vascular Erectile Dysfunction Treatment

The therapeutic interventions aim at improving the blood flow to penis:

Phosphodiesterase type-5 inhibitors (PDE-5):  These are oral medications employed as the first line of therapy. They inhibit the enzyme phosphodiesterase that degrades cGMP, thus augmenting the cGMP-based vascular smooth muscle cell relaxation and the subsequent blood flow into penis.

• Intercavernosal Injections: It injects drugs such as prostaglandin E2, papaverine, atropine, and phenyltolamine into the corpora cavernosa located at the base of the penis. These drugs are vasodilators that expand vessels for higher blood influx into penis.
• Intraurethral Medication/Suppositories: It includes insertion of a vasodilator tablet in the urethra, widening the vessel diameter.
• Vacuum Devices: A vacuum pump creates negative pressure that drives blood flow within penis.
• Penile Prosthesis: It is a surgically invasive procedure where a prosthetic device is placed inside penis to restore erectile functions.
• Balloon angioplasty: It is a minimally invasive procedure that widens the vessels by inflating a special balloon within them, with or without placement of stent to prevent vessel narrowing.
• Surgical Intervention: These include penile revascularization surgery and venous surgery that ligates vessels to bypass blocked artery or reduce venous leakage.

Limitations of ED Treatment

Although the above-mentioned treatments are effective, they suffer from setbacks listed below.

• Some treatment options show side effects. For instance, there have been reports of blindness, deafness, indigestion, etc., with PDE-5 inhibitors, whereas penile prosthesis can cause severe infections.
• These treatments are not effective in all patients. The success rate of PDE-5 inhibitors is 76%.
• These treatments demonstrate minimal long-term benefits.

Stem Cell Treatment For Vascular ED

Stem cell discovery has been a noteworthy advancement in the medical field. These cells target cellular-level pathways of disorders and regenerate tissue. They drive repair and recovery, restoring the health of the tissue or organs. Among many Stem Cells, Mesenchymal Stem Cells (MSCs) are the preferred choice due to their high accessibility and negligible ethical considerations. Stem cells used for ED treatment works on the following pathways:

• Cell Regeneration: Stem cells transform into different cell types- endothelial cells and smooth muscle cells. They replenish the depleted cells and improve tissue function.
• Angiogenesis: Stem cells stimulate blood vessel remodelling by releasing growth factors like vascular endothelial growth factors (VEGF) and angiopoietin 1, IGF-1, bFGF, etc.
• Anti-inflammation: These cells counter inflammation by elevating TSG-6 and anti-inflammatory cytokines.
• Nerve Regeneration: They release factors such as NGF, nNOS, etc. that protect nerve cells and regenerate them for functional recovery.
• Antioxidant: These cells overexpress PRDX2, which mitigates oxidative stress and prevents cellular damage.

Stem cells diminish hypoxia in endothelial cells and prolong the survival of vascular cells, which reinstate vascular flow and erectile functions.

Vascular Erectile Dysfunction Treatment Success Stories

Clinical Evidence

• Demour et al. conducted a phase 1/2 clinical trial in 2021 and evaluated the treatment of 22 ED patients with umbilical cord MSCs. The study revealed significant improvements in erectile function, rigidity of erection and vascular flow within 6 months.
• Levy et al. administered stem cells to 8 ED patients and showed improvements in vascular flow after 3 months. Patients were able to achieve an erection.

In terms of safety, trials reported no serious adverse side effects of stem cell infusion except pain, redness, bruising, or irritation at the injection sites. 

Conclusion

The prevalence of vascular ED has been increasing with age and comorbidities such as diabetes, hypertension, etc. The current treatment modalities are not effective in several individuals and might cause side effects. Moreover, none of the treatments provides lasting effects by targeting the pathways behind the disorder. Stem cells address these concerns by modulating core mechanisms of the disorder. They treat the disease without causing any adverse effects, as per clinical trials. Their effects last for more extended periods increasing the blood flow to penis and resolving the issue from the root. Advancells understands the impact of vasculogenic ED on one’s life and provides high-quality stem cells potent for ED treatment to improve the quality of life.

FAQs

Q – What is vascular ED?

Vascular ED is caused by reduced blood flow to penis due to obstruction in arteries, blood vessel damage, or leakage via veins.

Q – What are the causes of vascular ED?

The low blood supply can occur due to various diseases that can damage blood vessels, such as peripheral arterial disease, cardiovascular disorders, obesity, aging, etc.

Q – How do stem cells cure ED?

Stem cells differentiate into vascular cells and also secrete growth factors that drive vascular remodelling, prolong cell survival and regenerate nerve cells.

Q – Why are stem cells better than the current treatment options?

Unlike current medications, stem cells target the root mechanisms of ED and deliver positive outcomes with lasting benefits.