Exosomes and Erectile Dysfunction

Erectile dysfunction is a common male disease and seriously reduces the quality of life of the patient and their partners. ED is considered a significant health issue. The current therapeutic modalities do not meet the needs of all causes of ED. Exosomes are a novel strategy that has been shown to have significant therapeutic benefit in the treatment of these cases.

Historically, erectile dysfunction was mentioned in the Egyptian literature greater than 5000 years ago. Worldwide, greater than 150 million men suffer from this illness, and it is projected to be a problem affecting more than 322 million by 2025. Organic pathology accounts for greater than 80% of the cases with the remainder being of psychiatric origin. Cardiovascular diseases, diabetes mellitus, dyslipidemia, hypogonadism and nerve damage are the leading causes of ED. ED is no longer just a problem of sexual dysfunction but can be the initial presentation of cardiovascular disease due to its vascular endothelial dysfunction.

The complex pathway that is involved in an erection has led to failures in the current pharmacological treatment. Failure rates with the current treatments reach 35%.

Mechanism of an Erection

Penile erection is a series of vascular events closely related to the smooth muscle cells and the epithelium of the corpus cavernosum. These cells form the basic structure of the sinusoids.

When smooth muscle is in a contracted state, the blood flow through the cavernous artery is restricted but the outflow through the venous plexus flows freely resulting in the flaccid state.

Upon sexual stimulation, nerve fibers release nitric oxide, which activates guanyl cyclase to increase the concentration of cGMP. (cyclic guanosine monophosphate)

Acetylcholine released from parasympathetic nerve fibers causes activation of adenylyl cyclase, resulting in an increased concentration of cAMP. (cyclic adenosine monophosphate)

High levels of cGMP and cAMP decrease intracellular calcium levels and lead to smooth muscle relaxation and this is followed by a normal erection.

If any of this process is interrupted, erectile dysfunction may happen.

Causes of ED

Cavernous nerve injury causes a decrease in nerve signals to the corpus cavernosa which reduces the nitric oxide level in smooth muscle. This can cause apoptosis in the smooth muscle and the endothelium of the blood vessels. This also upregulates fibrogenic cytokines and forms collagen deposition in the smooth muscle. These functional and structural changes lead to veno occlusive disease and ED.

Hypoxia can cause a decrease in prostaglandin E1 levels of the corpus. Normal levels inhibit profibrotic cytokines and when not inhibited they enhance collagen deposition, decreasing smooth muscle fibers, and change the overall elasticity of the penis. The ability of the corpus to compress the veins are then impaired.

In diabetes, the elevated glucose levels elevate oxygen free radicals which impairs the synthesis of nitric oxide and cGMP.

Studies have shown the beneficial effects of transplanted regenerative tissues in the treatment of erectile dysfunction. These tissues can differentiate into specific cells that have lost function due to disease states or trauma.

Exosomes are small membrane bound extracellular vesicles which can carry various bioactive substances. Exosomes contain many bioactive proteins, such as metabolites, proteins, lipids, and nucleic acids. Exosomes have been proven to serve multiple physiologic and pathologic functions due to their intracellular communication. They either fuse directly with the plasma membrane of the recipient cells to transfer cargoes or interact with the receptors of the cells to activate signaling pathways and actually take part in the biogenesis in the recipient cells. Exosomes have been shown to promote functional recovery by facilitating angiogenesis and neurogenesis. Therefore, exosomes provide tissue structure of the corpus cavernosum and would ameliorate erectile dysfunction.

The antifibrotic action of exosomes would also aid in blocking the fibrotic action of TGF-B1. Exosomes could be a treatment for Peyronie’s disease because of this quality to block fibrosis in the corpus.

In other studies, the vasculogenic action in ED is induced by artery injury and the release of reactive oxygen species leading to cell apoptosis. This oxidative stress in the penis is a primary cause of ED. The administration of exosomes inhibited fibrosis and apoptosis ensuring functional endothelial action and that of the smooth muscle.

The action of nitric oxide and cGMP as described above is of primary importance in the function of erection. Song et al reported that exosomes upregulated the NO/cGMP pathway to ameliorate ED. The levels of these two substances, critical in the pathway for erection, were significantly increased after treatment with exosomes.

ED is considered as one of the long-term complications of diabetes. The risk of developing ED with diabetes is 2.5-fold. More than 50% of diabetes are affected with ED. Diabetes affects the levels of androgens, inflow of the arteries, outflow of the veins as well as nerve function in the penis.

In an animal model built to mimic diabetes mellitus, three studies constructed an ED model by damaging the cavernous nerves surgically. Administration of exosomes demonstrated structural changes post injection. The structures, damaged to demonstrate ED were restored which indicated amelioration of the endothelium and the smooth muscle action in the body of the corpus cavernosum. The exosomes again demonstrated the ability to inhibit fibrotic changes and apoptosis.

Admittedly, more studies are needed to standardize the protocols for this novel treatment of erectile dysfunction. However, exosomes will not cause immune tolerance or cell malignancies. While exosomes may not completely reverse the pathological changes in the corpus cavernosum, they can delay progression of the disease which can increase the quality of life in

these patients. Also, exosomes are compatible with other treatment modalities and can be combined with other treatments in which the combination may be more effective in some refractory cases. (combination with platelet rich plasma and exosomes)

Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA cleared and designed for safety, sterility and effectiveness. Our kits are scientifically manufactured to provide a platelet concentrate, devoid of red blood cells with a minimum number of leukocytes, critical to the regenerative process. Platelet Rich Plasma has been proven to be efficacious in the treatment of erectile dysfunction and can be combined with exosomes for an added benefit.

Juventix Regenerative Medical is proud to announce our collaboration with Evolutionary Biologics to offer exosomes and other regenerative products for the regeneration of tissues and tissue-based therapies.