Are stem cell therapies a treatment alternative for ED

Erectile Dysfunction is a disease which affects millions of men worldwide causing a huge loss of quality of life for the patients. It´s causes are numerous, ranging from physical to psychological issues which ultimately lead to ED. Several treatments for erection problems do exist but no cure for the underlying disease are available which completely restore quality of life. The following chapters summarise current knowledge on ED, standard and alternative therapies and how they are used as therapeutic regimen in clinical trials.

Erectile Dysfunction (ED) is one of the most prevalent sexual health conditions worldwide. Due to the fact that most affected men are not talking about their issues, there are only estimations of how many men are suffering from ED but for the US alone 18 million are estimated ^I. The official definition of ED is the “consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual activity” causing significant loss of quality of life ^II. Sexual arousal, a prerequisite for an normal erection, is quite complex and includes interaction from your brain, hormones, emotions, muscles, blood vessels and nerves. Physical and psychological issues are also intertwined as e.g. a minor physical problem that slows sexual response can lead to anxiety, which causes a complete erectile dysfunction. Physical conditions can include heart diseases, diabetes, obesity, tobacco use or diseases affecting nerves, like Parkinson´s disease, Multiple Sclerosis and others. Especially drug abuse (tobacco, alcohol and others) and obesity are well-known risk-factors for acquiring ED ^III.

As the reasons for ED are so numerous and a combination of physical/psychological reactions, there is no perfect way to overcome ED. Current standard therapies focus on treating ED with ^{III, IV}:

1. Oral phosphodiesterase 5-inhibitors (PDE5I). The famous “blue pill”, originally developed for treating heart diseases, increases the physical response to sexual arousal, causing a faster and stronger erection. If the reason for ED is anxiety and lack of self-confidence, this might be overcome with this treatment after a while.
2. An erection without sexual arousal can be induced by applying alprostadil either as injection into the penis or with a crème. As the induced erection is artificial, it can last longer than needed, causing side effects if it lasts too long (>1hour).
3. Mechanical support like vacuum pumps and penile implants. These invasive procedures might be necessary in case nerves are damaged already or sexual arousal is lacking. For obvious reasons the quality of life is still reduced with these methods.

There is no cure for ED by simply applying a standard therapy which is why mostly the symptom ED itself is treated to be able to have sexual intercourse. While PDE5I treatment is easy to be applied, its use still needs to be timed properly, while the other options are nothing one can include easily into sexual foreplay. Therefore, all current treatments need to be timed properly and quality of life is still affected.

A treatment that increases erectile function for a longer time without thinking about how and when to have sex is still lacking, even though treatments with L-Arginine are promising. Many different results have been published on L-Arginine but nowadays it is commonly agreed that the consumption of high dose L-Arginine can increase the overall Nitrogen-Oxide-concentration in the body, which is essential for gaining an erection but only sufficient enough for mild to moderate ED ^V. Nevertheless, there is no clinical study on potential side effects of consuming high doses of L-Arginine over a longer time, which might be a high risk just to “be ready”.

The following alternative treatments are available even though most of them are still experimental ^IV:

1. Therapies using physical energy to induce local neovascularisation. Low-intensity extracorporeal shockwaves or low-intensity pulsed ultrasound is applied over a certain time (treatment regimens in studies differed between 2-3 weeks) ending in an increased erectile hardness score for most of the patients for several month.
2. Several products are available which are focused on increasing NO to provide a proper basis for a natural erection. Besides the already mentioned L-Arginine, L-Citrulline is investigated which is biochemically converted to L-Arginine inside the body but seems to show even better effects than taking L-Arginine directly. Herbal supplements like Ginseng or Yohimbine have been investigated intensely but no significant effect versus placebo groups could be detected. Nevertheless, as ED is often partially psychologically, the placebo effect alone might be already enough, depending on the grade of the ED.
3. Stem cell based therapies are available as well using different approaches to achieve the same outcome. They are discussed in detail in the next section.

Stem cells are well-known for their potential to differentiate and grow during our whole life, constantly replenishing various cell types. Those cells are mainly localized in our bone marrow but also in some other niches within our body. Since scientist revealed the potential of these immortal cells, they have been within focus for the development of certain technologies. The idea behind using stem cells to treat ED is based on their ability to secrete compounds which can support the surrounding tissue in their functionality. To date, there are two main approaches:

1. Stem cell therapies. The treatment of ED with injections of stem cells has been investigated over the last decade, mostly focused on animal experiments. The first clinical study in 7 men was published in 2010, in which stem cells had been introduced by cavernosal injections. Although the mode of action is still unknown, 3 out of these 7 men regained morning erections and 2 were able to have sexual intercourse when using PDE5I support. Different follow-up clinical studies applying stem cells of different sources or with different treatment regimens were equally promising, increasing the erectile function in some men of the treated group, but the underlying causes are still under investigation. As of today, there are 4 actively recruiting clinical studies listed which intend to use stem cells for treatment of ED (NCT04972890, NCT04594850, NCT03933995, NCT05147779).
2. Platelet-rich Plasma (PRP). PRP is harvested from the patients blood and processed for the final product. For details on what PRP is and how it is generated at ANOVA IRM for other indications, please follow this link. The treatment of ED with PRP by cavernosal injections has so far been shown with significant effect only in animals. Only two human trials are filed online which used PRP to treat ED and their conclusions are mediocre at best. One open clinicial trial is scheduled at the moment that intends to further study PRP in combination with shockwave therapy to treat ED (NCT05048667). Nevertheless, the use of PRP as a promising new experimental therapy is sold already, although there is no clinical evidence for its significance.

Scientists are discussing the results, trying to explain the outcome mainly by enhanced tissue repair and functionality, induced by the injected stem cells. It is a common agreement though, that most effects caused by stem cells are mediated via released proteins into the environment of the cells, not by direct cell-cell interaction. As stem cells are pluripotent and could in principle also develop into cancer cells, it appears to be a great risk to inject these cells only to be able to have sex again. This risk is not given when using the ANOVA secretome for ED treatment.

Stem cell isolation, their cultivation and in vitro expansion are quite complex procedures, especially if they are meant to be reinjected in vivo. On the one hand, the risk of contamination and subsequent rejection of the cells might occur. On the other hand, cells that are expanded too rapidly might loose their potency or might transform into cancer cells if treated with complex cocktails of growth factors for too long. Hence, the whole process must be strictly controlled throughout the whole life cycle of the cells, from isolation to reinjection or the therapy might cause adverse effects or be simply ineffective. The ANOVA secretome, in contrast, is fully licenced by the German drug authorities and is very safe alternative.

Stem cell isolation, their cultivation and in vitro expansion are quite complex procedures, especially if they are meant to be reinjected in vivo. On the one hand, the risk of contamination and subsequent rejection of the cells might occur. On the other hand, cells that are expanded too rapidly might loose their potency or might transform into cancer cells if treated with complex cocktails of growth factors for too long. Hence, the whole process must be strictly controlled throughout the whole life cycle of the cells, from isolation to reinjection or the therapy might cause adverse effects or be simply ineffective. The ANOVA secretome, in contrast, is fully licenced by the German drug authorities and is very safe alternative.

The secretome provided by ANOVA IRM contains exosomes and soluble secreted factors and is fully legally controlled. It does not contain cells that carry the risk of malignancy as it is proven cell-free. ANOVA IRM was the first institution world-wide to acquire legal permission by the regulatory bodies for this type of product in 2018.

Only one donation is necessary to isolate your own personal, so-called autologous, mesenchymal stem cells from belly fat which are then cultivated in vitro for a short period to generate sufficient amounts of minimally-manipulated stem cell-conditioned medium which contains the exosomes and soluble factors secreted by your stem cells. After separating the stem cells from the medium, your own personalized secretome will undergo a thorough pharmaceutical quality control before it is being used for up to 10 treatments, which will be scheduled according to your special needs, usually in parallel to the 3 months HAL training period. All internal processes are controlled by German Drug Authorities and are therefore highly regulated to yield proven quality and highest safety available.

There are many advantages when using the ANOVA secretome over the injection of stem cells. As the stem cells are cultivated over a short period of time and under mild conditions there is only a low risk of loss of potency during the cultivation. No cells have to be reinjected and therefore the risk for infections or the risk to develop cancer from the pluripotent stem cells does not exist. Your own personalized secretome-containing medium will be generated and stored until you need it. The freezing does not largely change the composition. In contrast, classical MSC treatments are 1 time therapies which does not seem reasonable, as stem cells are not a cure and therefore, on-going treatment is needed. If stem cells are frozen, their behavior seems to change rendering them potentially less effective which does not allow for freezing for repeated therapy. Finally, you can rely on the highly regulated system of the German Drug Authorities when it comes to quality and safety of the final product.

Whether Stem Cell Secretome is a treatment option for you depends on your current health status and the underlying problem in your specific case. If you would like to know more about your treatment options with Stem Cell Secretome, schedule an appointment today. Our scientists and doctors will assess your medical files to see if you can benefit from stem cell treatment.