Erectile dysfunction improvement using mesenchymal stem cells

Erectile dysfunction (ED) is the inability to achieve and maintain an erection suitable for sexual intercourse. It is estimated that about 1 in 10 adult men will experience ED in their lives, mainly affecting men over the age of 40. The incidence of ED is 1-10% in men younger than 40 years of age [1]. Common reasons are drinking too much alcohol, stress, relationship problems, or being too tired. They affect psychology and the quality of family life. That’s why we need appropriate therapies to help improve this problem. Stem cell therapy brings hope and confidence in the treatment of ED.

What are the causes of erectile dysfunction (ED)?

There are many causes of ED, such as [2, 3]:

• Vascular disease: The blood supply to the penis can become blocked or narrowed because of vascular disease such as atherosclerosis (hardening of the arteries).
• Nerve disorders (such as multiple sclerosis): The nerves that send impulses to the penis can be damaged by stroke, diabetes, or other causes.
• Psychological states: These include stress, depression, lack of stimulation from the brain, and performance anxiety.
• Prostate, bladder, and colon chronic diseases or cancers may also contribute factors.
• Medications that can cause ED: ED is a common side effect of some prescription medications, which can affect a man’s hormones, nerves, or blood circulation, leading to ED or increased risk of the syndrome. Common medications that can list ED include diuretics (medications that increase urine flow), antihypertensives (high blood pressure medications), Antihistamines, Antidepressants, Disease medications for Parkinson’s disease, Antiarrhythmic drugs (drugs to treat abnormal heart activity), Hormones, Prostate cancer drugs.

How to treat erectile dysfunction?

Depending on its causes, there are many ways to treat ED, including [4-7] oral medications, sex therapy, penile injections, vacuum devices, intraurethral medications, and surgery (penile implants). In addition, we can intervene with non-surgical treatments for ED, such as Physical activity and education about sex, sexual behavior, and sexual response, which can help a man overcome being over-concerned about sexual dysfunction. It can perform several methods of implant surgery. However, there are potential risks of infection, side effects, and difficulty performing sexual intercourse. Therefore, researchers and medical professionals need to develop more promising and safer methods to help improve the sexual satisfaction of couples while addressing concerns about sexual dysfunction. Stem cell therapy has great promise and is increasingly being researched and tested. Stem cell therapy is a new treatment with regenerative abilities that can treat ED.

ED is one of the most common complications of diabetes in men, hindering the patient’s quality of life. Existing treatments, while only improving symptoms, cannot repair the affected tissues. Stem cells can regenerate and repair damaged penile tissue and endothelial cells in ED patients. Recent studies have provided promising results regarding the use of stem cells to treat this condition.

Clinical testing on animals

A study evaluated the effectiveness of administered bone marrow mesenchymal stem cells (BM-MSCs) for improving erectile function in rats with diabetic ED. Researchers infused MSC cells into mice with erectile dysfunction [8]. Four weeks after injection, erectile function was determined by measuring pressure in the penis. Penile tissues were collected for immunohistochemical analysis. The MSC-injected group showed a significant improvement in erectile function, as evidenced by the increased tissue expression in the penis. Thus, using MSC helps increase effectiveness in treating erectile dysfunction.

Another study examined whether treatment with adipose-derived mesenchymal stem cells (AMSCs) for diabetes-induced erectile dysfunction (DED) [9]. AMSCs were pre-treated with normoxia or hypoxia. Hypoxia exposure up-regulates the expression of several cytokines involved in angiogenesis and neuroprotection in AMSCs, including vascular endothelial growth factor and FIK-1 receptor, angiotensin (Ang- 1), basic fibroblast growth factor, glial cell-derived neurotrophic factor, stromal-derived factor-1, and CXC4 chemokine receptor. The results showed AMSCs treated in a hypoxic environment were effective in enhancing their therapeutic effect on DED, which may be because of their enhanced angiogenesis and neuroprotection.

Clinical trials

Recent studies have focused on stem cell therapy for ED in humans. Levy et al. reported the use of PM-SCs (placental stem cells) in eight people with ED [10]. After six months of treatment, the authors concluded that stem cell therapy improved erectile function. Another registered phase I clinical trial (NCT02945462) is the first to use two consecutive autologous bone marrow-derived mesenchymal stem cell (BM-MSC) transplants to treat diabetic ED. The primary outcome was to evaluate the safety and tolerability of autologous BM-MSCs. Four diabetic patients with ED participated in the trial. The researchers performed two consecutive injections of autologous BM-MSCs. Immediately, the researchers evaluated the tolerability, and after 24 hours, they assessed the safety for a duration of two years. Efficacy was assessed by the International Index of Erectile Function (IIEF) and Erection Hardness Score (EHS) over 12 months. The procedure was tolerated well, and no patients reported significant side effects. There was significant improvement in IIEF and EHS; IIEF, Erectile Function, Sexual Desire, Intercourse Satisfaction, and General Satisfaction. This is the first human study to show the tolerability, safety, and efficacy of intracavernosal injection of autologous BM-MSCs to treat diabetic patients with ED. [11].

Bahk and colleagues conducted a study on 7 ED patients aged 57-87 years and compared the effectiveness of stem cell treatment with three patients receiving erectile dysfunction treatments, such as PDE5 inhibition [12]. The stem cells used were umbilical cord-derived mesenchymal stem cells at a dose of 1.5×107 cells injected intravitreally. Researchers followed this study for nine months and found that the stem cells produced a positive effect on erectile dysfunction. This was observed through improvements in the scores of assessments, such as IIEF-5, SEP, GAQ, and erection duration.

Protogerou et al. reported another approach using autologous adipose tissue stem cells to treat ED in 5 people with diabetes. This group was compared with five other controls. The number of stem cells provided is 2×10⁵ cells in 3 months. At the end of the study, the author noted significant improvements before and after stem cell treatment [13].

Another clinical trial with allogeneic stem cell transplantation (ClinicalTrials.gov registration code is NCT02945449): Use of 2 consecutive injections of umbilical cord-derived mesenchymal stem cells of the Wharton’s jelly class (WJ-MSC) was studied in the treatment of diabetic patients with ED. The primary outcome was to assess safety and tolerability, and the secondary outcome was to assess the efficacy of 2 consecutive injections of allogeneic WJ-MSCs in the ED for diabetic patients [14]. Twenty-two diabetic patients with ED were part of the study. Tolerability was assessed immediately, and after 24 hours, safety was assessed for 12 months. Efficacy was assessed using the International Index of Erectile Function-5 (IIEF-5), EHS, and Color Duplex Ultrasound over 12 months. After a period of treatment, the stem cell sample was well tolerated. No patients reported serious side effects. There have been significant improvements in IIEF-5, EHS. The authors found this to be the first human study with good tolerability safety and demonstrated the efficacy of allogeneic WJ-MSC injection to treat diabetic patients with ED.

Another preclinical study using bone marrow-derived mesenchymal stem cells (BMSCs) to treat ED showed promising results. The authors conducted a Phase 1 clinical trial with autologous BMSCs in patients with ED because of radical prostatectomy or diabetes. Ten patients (5 with post-prostatectomy ED and 5 with diabetes-related ED) could not perform normal sexual activity [15]. The brief clinical trial was registered with the US National Institutes of Health on ClinicalTrials.gov (NCT02344849). The results demonstrate the safety of stem cell therapy and its ability to improve ED. In the clinical trial, we screened 13 patients, enrolled 10 patients, and administered autologous BMSCs to them. Out of the enrolled patients, 9 successfully completed the trial. One patient with post-prostatectomy ED experienced two adverse events (fever and back pain), and two patients with diabetes-related ED experienced five adverse events (one case each for viral upper respiratory tract infection, prostatitis, itching, and two cases of hyperglycemia). Of these patients, one with diabetes-related ED experienced two serious adverse events (two cases of hyperglycemia). All adverse events were unrelated to autologous BMSC therapy. In addition, laboratory tests and vital signs did not show any clinical significance in terms of other safety measures. The mean score of the International Index of Erectile Function increased significantly in one month compared with the baseline. This Phase 1 clinical trial confirmed the safety and potential efficacy of autologous BMSC therapy in patients with ED. However, a phase 2 clinical trial still needs to confirm the authors’ results.

The above findings show that using stem cells brings excellent results for patients with erectile dysfunction. This is a promising and safe therapy for ED patients, helping to improve men’s sexual function. From there, it brings many positive factors in family and social life.

References:

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