Mesenchymal Stem Cells for Erectile Dysfunction (ED)

Of all the animals on earth, probably only human males have the need for aphrodisiacs. Because most male mammals have a penis bone.

The penis bone is located at the end of the penis, ranging from less than a millimeter to nearly a meter. Animals with their own penis bones not only do not know what impotence is, but they can also achieve a powerful delaying effect to a certain extent.

However, humans are the only primates without a penis bone. This forces men to embark on a long road to pursue erection and delay. Where there is demand, there will naturally be a market, and there is no doubt that the market for male enhancement is huge.

The first dream, food supplements!

"Treat the disease if it is sick, and strengthen the body if there is no disease." The first thing that businessmen think of is the theory of food supplements and aphrodisiacs . In an era when there was no internet celebrity food marketing, having an aphrodisiac buff in itself was enough to make a food popular.

It is said that Casanova ate 40 oysters a day in order to maintain his sexual performance. After that, the so-called aphrodisiac effect of oysters spread, and gradually became a sacred aphrodisiac that is famous in Europe and Asia.

A report in 2005 stated that scientists discovered ingredients in bivalve shellfish that can stimulate sexual desire-the compounds D-aspartic acid and N-methyl-D-aspartic acid. It also stated that in animal experiments, these two compounds were confirmed to increase the levels of sex hormones in experimental mice.

Of course, the compound content in the experiment exceeds the combined content of 200 oysters - you may have to eat 5 times more oysters than Love Saint to meet the efficacy. In addition, the zinc element in oysters is often extracted to support the aphrodisiac effect. Although zinc does have a certain relationship with reproductive system health. It can promote the normal development of male organs and maintain the activity of sperm. However, what if you want to improve your sexual performance by eating leeks to obtain the zinc contained in them? Sorry, there is currently no scientific evidence to prove this is possible.

Although eating oysters and leeks has little effect on improving sexual performance, if the body is deficient in zinc, you can take the opportunity to supplement it, which will have some effect. However, there are many ways to supplement zinc, and it is not necessary to eat leeks.

To this day, no food has been scientifically proven to have clear aphrodisiac and aphrodisiac effects, but aphrodisiac recipes are growing continuously, such as Indian peppers, French bamboo shoots, Japanese loaches, and Arabs' beef and mutton.

Unwilling to explore and make up for the shape!

Of course, there is also a more fantasy concept of nourishing food to strengthen yang - using "shape" to supplement "shape".

The so-called "form" complements the "form", that is, eating food that is similar in appearance to a certain organ of the human body is beneficial to that part of the human body. Column-shaped foods that vividly resemble male external genitalia are the first to become aphrodisiac eaters' dishes.

Cynomorium cynomorium, Cistanche deserticola, matsutake mushroom, iron rod yam, sea cucumber, geoduck, etc. are all considered to be aphrodisiacs. It is no exaggeration to say that if cucumbers were only produced in a few areas and the output was scarce, they would be crazily packaged as an aphrodisiac.

However, the imitation show will never be as popular as the real whip show, just like the star's stand-in will never be as popular as the star himself. Aphrodisiac diners have long been dissatisfied with portraits and have turned their attention to the lower bodies of animals. Bull whips, horse whips, deer whips, tiger whips, fur seal whips, seal whips, etc., have been taken off from various animals and entered into the mouths of humans.

So has the aphrodisiac effect been achieved? The external genitalia and even the testicles of male mammals do contain higher concentrations of male hormones, but as a steroid hormone, they are easily broken down in high temperatures. Therefore, after being cooked and eaten into the human stomach, the various whippes are no different from other proteins and fats.

Even if you are lucky enough to supplement some male hormones, it may lead to hormone imbalance in the body, cause endocrine disorders, and worsen the condition, which is really not worth the gain.

Strengthening yang and nourishing kidneys are naturally a two-pronged approach to maximize the effect. No, in addition to various whips, people's enthusiasm for using "shape" to supplement "shape" also extends to various kidneys. However, eating animal kidneys to strengthen yang and nourish kidneys is simply a false proposition. The animal kidneys that produce urine have little to do with improving human sexual performance, but they taste good as a delicacy.

But don’t underestimate mankind’s belief in aphrodisiac. Any food that can evoke associations with "sex" can be packaged as an aphrodisiac. As long as there are people in this world who want to strengthen yang, merchants will say that everything can be used to strengthen yang.

Viagra

It was not until the 1990s that Viagra came out, saving millions of male compatriots. Sildenafil, the main component of Viagra, can indeed help impotent men temporarily restore normal penile erection, allowing them to have smooth sexual intercourse. However, the effect of Viagra is one-time and lasts only a very short time. After 4-8 hours of taking effect, the effect of the drug will gradually dissipate, allowing the patient to quickly return to his original shape. This is obviously not friendly to some people who need to take Viagra for a long time.

In addition, patients generally face an anxiety: will drug resistance develop as the medication time is prolonged? Will it have no effect? So how can we treat both the symptoms and the root causes and break the "glandular" system?

The next stop, stem cells

Stem cells are the origin cells of life, maintaining the body's organ functions and metabolism, and can be used to treat more than 200 types of diseases such as diabetes, liver cirrhosis, kidney failure, and osteoarthritis. With the widespread application of stem cells, their properties such as "repairing the body and delaying aging" are gradually being included in the new generation of luxury aphrodisiac packages by "industry insiders".

As a new stem cell drug research and development company, we have something to say about “stem cell aphrodisiacs”. The application of stem cells must follow modern scientific standards, and modern Western medicine theory means not only knowing "what it can do", but also "why it can be done". What is the mechanism?

Most of the "non-ejaculation" cases in modern men are not simply physical problems, but a disease: erectile dysfunction (ED) is at work.

Research has found that the causes of erectile dysfunction can be divided into:

1. Psychological ED

Erectile dysfunction is caused by mental and psychological factors such as tension, stress, depression, anxiety, and marital discord. Such as anxiety and depression psychological disorders and environmental factors caused by incoordination in the daily relationship between husband and wife, lack of sexual knowledge, adverse sexual experiences, life, work or financial pressure, misunderstanding of media propaganda, fear of diseases and side effects of prescription drugs, etc.

2. Organic ED

● Vascular causes: Vascular lesions are the main cause of ED, accounting for nearly 50% of ED cases, including any disease that may cause reduced blood flow in the cavernosal arteries of the penis, such as atherosclerosis, arterial damage, arterial stenosis, and pudendal arteries Shunting and cardiac dysfunction, etc., or penile venous leakage caused by reduced smooth muscle in the tunica albuginea of ​​the penis and the cavernous sinus of the penis, which hinders the closure mechanism of venous return. Almost all risk factors that can cause hypertension, such as smoking, hyperlipidemia, obesity, etc., can increase the incidence of ED.

● Neurological causes: Central and peripheral nerve diseases or injuries can lead to erectile dysfunction. Central causes include stroke, tumor, Parkinson's disease, myelopathy, lumbar disc disease, multiple sclerosis, and multiple atrophy; peripheral neuropathies such as Diabetes, alcoholism, uremia, polyneuropathy, etc.

●Surgery and trauma: major vascular surgery, pelvic or retroperitoneal surgery or trauma, such as radical prostatectomy, abdominoperineal radical resection of rectal cancer and other surgeries, as well as pelvic fractures, lumbar compression fractures or straddling injuries, can cause penile erection-related problems. Damage to blood vessels and nerves, leading to erectile dysfunction.

● Endocrine disorders, chronic diseases and long-term use of certain drugs: such as hypogonadism, thyroid disease, acromegaly, any disease that causes lower blood testosterone levels and changes the function of the hypothalamic-pituitary-gonadal axis, drugs such as anti-elevated drugs Blood pressure drugs (diuretics and beta-blockers), antidepressants, antipsychotics, antiandrogens, antihistamines, and drugs (heroin, cocaine, methadone, etc.) can all cause erectile dysfunction.

● Diseases of the penis itself: abnormal anatomy or structure of the penis, such as Peyronie's disease, micropenis, penile curvature deformity, severe phimosis and balanitis.

The treatment of erectile dysfunction (ED) also starts with stem cells

After stem cells enter the patient's body, their own "homing" characteristics allow them to accurately reach all directions that affect the male reproductive mechanism and need repair, and perform comprehensive repairs.

It not only promotes vascular regeneration and nerve repair of the corpus cavernosum of the penis, but also fundamentally increases the blood supply speed and volume of the dorsal artery of the penis to the corpus cavernosum of the penis, and enhances the hardness and size of erection by at least 1-3 cm.

A research team led by Dr. Martha Haahr from Odens University Hospital in Denmark reported the results of a phase I clinical trial using mesenchymal stem cells to treat ED at the 32nd Annual Meeting of the European Association of Urology. Clinical trial results showed that 21 patients' ED symptoms were improved to varying degrees, and 38% of patients' erectile dysfunction completely returned to normal.

In addition to erectile dysfunction (ED), stem cells can also treat Peyronie's disease (fibrous cavernitis).

Penile fibrous cavernitis is mostly suffered by middle-aged people, mainly between the ages of 45 and 60. It can be divided into acute phase and chronic phase. The former is characterized by acute inflammatory reaction and pain, which mainly occurs when the penis is erect. 30% to 40% of patients have obvious pain symptoms. The acute phase can last for several months, during which nodules can form on the penis and the penis continues to bend toward the affected side. When the active inflammation of the tunica albuginea of ​​the penis stops, it enters the chronic phase. During this period, the pain symptoms usually disappear, plaques form induration, and the curved penis cannot recover.

Most penile fibrous cavernositis is an insidious disease. Patients are not satisfied with their erectile function, find painful plaques on their penis, and their penis curvature progresses slowly. There are also cases of sudden onset, where the penis is suddenly found to be bent, which generally does not progress. Curvature and deformation of the penis cause difficulty in sexual intercourse. If there is an impotence fistula, there is a psychological disorder or organic disease of the penile blood vessels. Induration or cord-like plaques can be palpable on the back of the penis, varying in size, single or multiple, with no or slight tenderness, and pain when the penis is erect. The lesions do not invade the urethra and there is no urination or ejaculation disorder.

The process of treating a bent and deformed penis is not as simple as breaking a bone. It only requires a small splint or a cast to immobilize it for a few months.

Previously, patients often required surgery to restore sexual function. But the risk of taking a knife to the "lifeblood" is too high. In addition to damaging and destroying the cavernous tissue of the penis, erectile dysfunction (ED) may also occur, and even aggravate or relapse the penis.

Existing treatments include drug therapy, physical therapy and surgical treatment, but the efficacy is not satisfactory, so the medical community turns its attention to stem cells.

Uros Milenkovic published a review report on the use of mesenchymal stem cells (MSC) in the treatment of fibrosis in the journal Nature. This article mainly summarizes the use of mesenchymal stem cells (MSC) in the treatment of Bellon's disease, urethral stricture and other diseases in the past 20 years. The therapeutic effects achieved, combined with preclinical research data, indicate that mesenchymal stem cells (MSCs) have good effects and great therapeutic prospects for the treatment of fibrotic inflammation.

As a safe treatment method, stem cell therapy has immunosuppressive, anti-inflammatory, anti-fibrotic and promoting blood vessel formation effects. It can inhibit the occurrence and progression of inflammation by secreting a variety of cytokines.

In other words, stem cells can inhibit other inflammatory diseases that may affect sexual well-being, including prostatitis and nephritis.

To sum up, stem cells can indeed help men improve their functions in some cases, but the reason is not because of fantasy expressions such as "replenishing qi and strengthening the foundation, tonifying the kidneys and storing essence, aphrodisiac and treating impotence", but because they have typical indications and usefulness. Have detailed clinical data and clear regulatory authorities.

It is unscientific and irresponsible to simply equate stem cells with "elixir of longevity" and "holy elixir of aphrodisiac". Globally, stem cells are regarded as the most advanced in the field of biopharmaceuticals. Through scientific and rigorous clinical trials, scientists from various countries are committed to developing new stem cell drugs and promoting stem cells to benefit the general public.

Progress of stem cell therapy in male sexual dysfunction

Stem cells are thought to be capable of differentiating into various cell types under specific conditions, including endothelial cells, smooth muscle cells, and neuronal cells. Intracavernous injection of mesenchymal stem cells ( MSC ) may replace damaged endothelial and/or cavernous smooth muscle cells. Other theories proposed include paracrine effects of MSCs following injection rather than direct replacement of damaged cells by cellular differentiation. There is research into the use of MSCs and the regulation of certain key mediators in the erection mechanism, including intracellular nitric oxide and calcium concentrations. Intracellular regulation of nitric oxide and calcium through the action of various transmembrane transport ion channels is considered a therapeutic target for stem cell therapy in ED.

Erectile dysfunction ( ED ), defined as the inability to initiate or maintain a satisfactory erection for sexual intercourse, is the most common male sexual disorder. The prevalence among men aged 40-70 years is about 50%, with nearly 15% of patients reporting complete erectile dysfunction and the remaining patients having varying degrees of erectile dysfunction. In recent years, the prevalence of ED due to cardiovascular disease, atherosclerosis, metabolic syndrome, diabetes, or prostate cancer has increased. Excluding psychogenic ED, organic ED is the result of physical damage to vascular, endocrine, neurological, and anatomical structures, all of which contain a complex network of structural pathways that require integration of signals from nerves, cavernosal muscles, and endothelium to restore the penis. erection. Figure 1 depicts a map of biochemical signaling at the cellular level during erection and the pathophysiology of ED.

Recent data suggest that the true prevalence of ED is greatly underestimated. This is particularly pronounced among the younger population, where the proportion is estimated to be as high as 10–30%. Additionally, and equally concerning, is the low proportion of patients diagnosed with ED who subsequently receive active treatment, with approximately half receiving medication specific to their condition. There are many drug treatments for ED, among which phosphodiesterase 5 inhibitors ( PDEi ) have become the most commonly used drugs because of their overall efficacy and few contraindications.

ED refractory to medical treatment is increasingly common today due to the emergence of the modifiable risk factors mentioned previously. More precisely, diabetic patients and postprostatectomy patients accounted for a large proportion of these PDEi non-responders. Nerve-sparing prostatectomy, despite new technologies such as robot-assisted surgery ( RARP ) and noble-sparing technology, may result in ED in up to 90% of patients undergoing prostate cancer surgery due to direct nerve injury or indirect neuropraxia.

Peyronie's disease, a chronic disease characterized by the formation of fibrous plaques in the tunica albuginea, leading to penile deformation associated with veno-occlusive ED, also represents a subset of PDEi non-responders. These factors cause irreparable damage to the primary physical mechanism responsible for erection; therefore, it seems plausible to hypothesize that PDEi, which act by enhancing intracellular signaling, are ineffective.

Over the past decade, new treatment modalities have emerged that are not only symptomatic but also have the potential to be curative. Among these new treatment modalities are shock wave therapy, platelet-rich plasma injections and stem cell therapy ( SCT ) . With the advancement of stem cell research, it is speculated that stem cells can differentiate into endothelial cells, nerve cells, and smooth muscle cells to replace penile structural tissue damage associated with ED. In vitro differentiation of these cell lines has shown promising results in preclinical settings in various animal models; however, the main source of their therapeutic efficacy appears to be related to their enhanced paracrine effects in peripheral tissues.

Stem cells from different sources have been used in several studies over the years. Mesenchymal stem cells ( MSC ) are the cell lines generated with the fewest ethical considerations compared to other cell sources and pose no cancer risk due to their genetic stability. MSCs can be obtained from a variety of cell populations present in organisms. Bone marrow stem cells ( BMSC ) , adipose stem cells ( ADSC ) , amniotic fluid stem cells ( AFSC ) , placental stem cells ( PSC ), and urine stem cells have all been used in clinical studies in animal or human studies for ED management.

The authors conducted a relevant literature search and compiled the most relevant available literature on the current status of mesenchymal stem cell therapy for ED management. Priority will be given to systematic reviews, clinical trials, and human studies. In the case of basic research reviews, primarily for the preclinical setting, the focus is on studies with in vivo experiments in animal models.

All studies are registered with ClinicalTrials.gov, including ongoing and completed clinical trials. Search PubMed with the keywords ( erectile dysfunction ) and ( stem cell therapy ) .

animal research

In 2004, Bochinski et al. first described the potential therapeutic benefits of neural crest-derived stem cells in a rat model of neurogenic ED. Since then, numerous preclinical studies have aimed to demonstrate the efficacy of stem cell therapy in the treatment of ED secondary to different causes: including aging, diabetes, hypertriglyceridemia, cavernosal nerve injury, and others. To date, there are four published meta-analyses covering the available evidence from preclinical studies.

In the first study, a final analysis of 12 included studies demonstrated the efficacy of stem cell therapy in a rat model of cavernous nerve injury ( CNI ) . Further subgroup analysis showed that the observed effects were not related to the simulated CNI model, but instead appeared to be related to follow-up time, stem cell source, and cell delivery method . Additionally, uncultured stem cells are less effective than cultured stem cells.

In 2017, Hou et al. further reviewed the existing evidence for the use of adipose-derived stem cells ( ADSC ) in rat models of ED other than CNI , including other etiologies such as diabetes, smoking, radiation therapy, and albuginea injury. Meta-analysis results show that the use of ADSC can regenerate damaged erectile tissue and contribute to the recovery of erectile function. Subsequent findings included a range of concomitant substances secreted by these cells, thus exerting a paracrine effect that significantly improved erectile function compared with ADSC alone in subgroup analyses . After identification, it was found that these substances include neurotrophic factors such as brain-derived neurotrophic factor, vascular endothelial growth factor ( VEGF ) , and hepatocyte growth factor.

Regarding the diabetic rat model, infusion of large amounts of ADSC (> 1×10 6 ), ADSC infusion combined with insulin treatment and previous ADSC hypoxic conditioning showed better results. Based on previous research in this field, Park et al. analyzed 19 studies in a meta-analysis published in 2019 with the aim of evaluating the role of ADSCs in CNI-induced ED rat models. Key findings showed that ADSC therapy improved erectile function based on penile hemodynamic parameters, intracavernosal pressure, and mean arterial penile pressure ratio ( ICP/MAP ) , and that ADSC was able to respond to changes in measured levels of nitric oxide synthase ( NOS ) Regenerates damaged tissue, cyclic guanosine monophosphate ( cGMP ) and smooth muscle to collagen ratio.

Similar results were described in a recently published network meta-analysis by Wani et al. To evaluate the role of stem cell therapy in erectile dysfunction secondary to cavernous nerve injury. Results including 29 animal studies and three human trials ( post-RP patients ) demonstrated significant increases in histological and molecular response parameters, including nNOS, smooth muscle content and anti-apoptotic activity in rats.

Preclinical studies have failed to elucidate the exact mechanism by which stem cell therapy exerts its therapeutic effects. However, a paracrine effect has been proposed that results from the combination of stem cells secreting growth factors with chemotactic, anti-inflammatory, regenerative, angiogenic and anti-apoptotic properties, favoring the regeneration of damaged tissue. Preclinical studies have shown that the use of stem cells improves vascular function in the cavernous endothelium and inhibits cavernous fibrosis while increasing the proportion of smooth muscle. Additionally, the use of ADSCs resulted in improved neurological function at the level of the corpus cavernosum, which is critical for maintaining erectile function , as well as reduced levels of apoptosis and inflammatory responses associated with increased risk factors for ED, such as diabetes or obesity.

During 2022, new preclinical research on stem cell treatment for erectile dysfunction was published, and new findings on markers of treatment response were made in several animal studies. Feng et al. observed reduced oxidative stress levels and tissue iron content in diabetic rats treated with UCSC, accompanied by overexpression of ferroptosis suppressor genes SLC7A11 and GPX4. Therefore, they concluded that stem cell therapy may exert part of its therapeutic effect by mitigating diabetes-induced ferroptosis .

Likewise, some studies published in 2022 have modified stem cell preparations or combined interventions aimed at enhancing their therapeutic effects. The efficacy of ADSC co-modification with VEGF and Smad7 was evaluated in a CNI rat model. Rats treated with co-modified ADSCs experienced more pronounced effects on erectile function.

human studies

Since 2010, a total of 23 interventional studies designed to evaluate the safety and effectiveness of stem cell therapy for the treatment of ED have been registered on ClinicalTrials.gov, and nine of these studies have been completed.

The main sources of stem cells for human therapy include bone marrow-derived stem cells ( BMSC ) and ADSC; however, a large number of studies have also used MSC derived from the umbilical cord ( UCS C ) and placenta ( PSC ) . The primary cell delivery method used in most published studies is direct intracavernosal injection, and most study protocols are designed in a similar manner.

First, the required stem cells need to be isolated from the patient's bone marrow tissue or fat ( fat cells ) in the case of an autologous transplant and from a healthy donor in the case of an allogeneic transplant. In most studies, consisting primarily of experimental Phase I/II clinical trials, the primary outcomes measured were tolerability and safety on overall effects on erectile function. In general, no serious side effects of MSC-derived ICI were found.

Umbilical cord (UCSC) and placenta-derived (PSC) stem cells

The first human clinical trial published by Bahk et al. In 2010, allogeneic UCSCs were used for the first time in an experimental setting to treat ED complicated by diabetes. Seven men aged between 57 and 83 years were each injected with 1.5 × 10 cells . Most patients regained spontaneous erections within one month, and these results were maintained during the 6-month follow-up period. Additionally, a decrease in blood glucose levels was observed two weeks after the start of treatment, which may explain the potential benefits of MSCs in diabetes treatment.

Safety of the treatment was not a measured outcome in this particular study; however, this was fully assessed in the later phase I clinical trial published by Levy et al. In this study, eight patients with complete PDEi unresponsive ED were followed for 6 months. Adverse effects as well as hemodynamic and functional outcomes of placental stem cell ( PSC ) therapy were analyzed . No serious adverse events were noted in the study, and an improvement in mean penile arterial blood flow was observed that was maintained for 6 months after initiation of treatment.

Bone marrow-derived stem cells (BMSC)

Yiou et al published a phase I/II clinical trial ( INSTIN study ) in which a total of 18 patients ( 12 in the phase I ) underwent radical prostatectomy. Dose-escalating ICI of BMSC was used. The authors concluded that single autologous BMSC ICI was safe and effective in patients with vasogenic ED; further improvements in erectile function and sexual satisfaction were observed at 6-month follow-up and maintained at 1 year. The complete mean follow-up period of 62.1 months confirmed the complete absence of adverse effects from the treatment; however, with regard to the results obtained in the first year after treatment, a slight deterioration in erectile function was observed. The authors also concluded that further cell injections may be needed over time to maintain therapeutic effects .

In another study, Bieri et al. in ED caused by diabetes and Al Demour et al. conducted two consecutive clinical trials in diabetic patients to explore the use of autologous BMSC and allogeneic Wharton's Jelly Stem Cells ( WJSC ) . Treat ED. In the first trial, BMSC's ICI was found to be safe and effective, with significant improvements in the International Index of Erectile Function ( IIEF-15 ) and Erectile Hardness Score ( EHS ) questionnaires . Second, the use of two consecutive ICIs of WJSC was explored for the first time in a total sample of 22 diabetic patients with ED. Positive results for tolerability, safety, and efficacy measured by IIEF-15 and EHS questionnaires and dual Doppler penile ultrasound imaging ( DPE ) were observed at 12-month follow-up .

Adipose-derived stem cells (ADSC)

As we mentioned before, another most studied source of MSCs for ED treatment is adipose tissue. ADSC are metabolically active cells that play an important role in the process of vascular reconstruction of damaged tissues, inhibition of apoptosis, and immune regulation. In a small study conducted by Garber et al. in 2015, a dose of 1.5 × 10 7 ADSC/person was injected into 6 diabetic patients. ICI consists of ADSC obtained after culture rather than isolated SVF. Four of the six patients regained spontaneous morning erections within a month and were able to have sexual intercourse with PDEi treatment in the last month after ICI for up to 12 months .

These results are consistent with those published by the Danish group led by Haahr, showing that ICI of autologous ADSC is a safe and effective treatment for ED patients after radical prostatectomy. No adverse events were observed at 12 months of follow-up. IIEF-15 score results improved significantly 6 months after treatment, and improvements persisted through 12 months. It is important to note that this improvement was observed in patients with normal preoperative erectile function and urinary incontinence at the time of inclusion . A phase III study ongoing and authorized by the same working group is now being studied in a larger sample of post-prostatectomy subjects.

Protogenau et al. proposed a technology for co-administration with ADSC. ADSC cultured suspended in platelet-rich plasma lysate ( PLP ) were administered and achieved certain results. Treatment improved erectile function without side effects at 1, 3, and 6 months of follow-up.

Other stem cell sources

A retrospective study by Ory et al analyzed the effects of transendocardial human mesenchymal stem cell ( hMSC ) injection of stem cells in the treatment of cardiomyopathy patients with erectile dysfunction. hMSCs can be derived from both autologous and allogeneic sources, and this study analyzed the first randomized, placebo-controlled data to examine the effects of SCT on erectile function.

The study by Zasieda et al. reported the use of mesenchymal stem cell-derived exosomes ( MSC-DE ) administered intravenously once a week for six weeks, MSC-DE injections combined with low-intensity shock wave therapy ( LISWT ) twice a week, 3000 shocks and 3 Hz Frequency. There was a significant increase in IIEF scores compared with baseline and a significant improvement in peak systolic velocity and a decrease in end-diastolic penile velocity after treatment.

In 2021, Mirzaei et al used stem cells isolated from the oral mucosa for intracavernosal injection at a dose of 50-60 million cells. The results of this randomized clinical trial with a control group concluded that intracavernosal stem cell injection improved sexual function and PSV and RI index of penile arteries in diabetic patients , with no observed side effects.

Finally, Koga et al. tested direct injection of stem cells from exfoliated deciduous tooth pulp ( SHED-CM ) . Results from 38 ED patients not treated with PDE5I or testosterone replacement therapy showed statistically significant improvements in IIEF-5 scores after three courses of SHED-CM treatment. However, no pathological evaluation was performed to accurately judge the effect of SHED-CM on vascular endothelial cells and its impact on follow-up. The safety of SHED-CM treatment and its potential to repair cavernous vascular damage represent a potential future treatment for patients with erectile dysfunction .

Ethical issues and limitations

ED is a urological disorder that has a severe psychological burden on those who suffer from it. Well-being, self-esteem, and social relationships are affected to varying degrees, as sexual functioning is an integral part of good personal health. Although the basic principles of ED treatment apply to all men, restoration of sexual function for the individual and his or her sexual partner must be considered on an individual basis. Therefore, these patients must be provided with measurable evidence and realistic expectations from treatment. In the specific area of ​​sexual issues, it is also important to consider the strength of the placebo effect. In studies published with a single arm, this effect should be seriously considered as a possible source of bias.

Stem cell therapy for ED can only be considered in an experimental setting. Despite repeated warnings from the European Medicines Agency ( EMA ) and the Food and Drug Administration ( FDA ) , this type of tourism has grown exponentially over time. The author believes that treatment outcomes in the field of ED are quite subjective ; therefore, these practices are more likely to be administered to a patient population with severe psychological and physical distress, resulting in unevidenced, unprofitable, and potentially dangerous interventions.

Preliminary Conclusions

In general, interventional studies of stem cell therapy to treat ED have shown promising results, with improvements in erectile function observed. These improvements can be measured by hemodynamic parameters ( mean penile arterial flow ) or by sexual function questionnaires ( IIEF-15 or EHS ) . Although most studies support the safety and therapeutic efficacy of MSC injections, existing studies are difficult to standardize.

The evidence to date mainly consists of small, open-label, single-arm trials using MSCs from different sources and with significantly different study protocols. Stem cell therapy is an experimental treatment modality. Due to their experimental nature, there is a lack of standardization of use and manufacturing, resulting in inter-laboratory variability in the handling of stem cells . Efforts should be made to optimize MSC manufacturing and processing, establish quality standards and promote legislative measures to obtain better homogeneous results.

To provide guidance for better and homogeneous manufacturing of MSC-focused therapeutic cell products, a review was recently published. The authors propose four critical steps in MSC manufacturing for their use as therapeutic products. These four steps include: appropriate donor selection, MSC harvest-isolation-expansion, storage-distribution and cell processing and other related issues . Because of the potential for placebo effect bias in studies involving self-perceived improvements in sexual function, larger comparative studies are needed. The intervention arm should not only be compared with placebo, but should also include treatment modalities that are already established in clinical guidelines to elucidate the true treatment effect. Further comparisons of different stem cell treatment modalities, such as cell therapy and cell-free therapy ( exosomes and SVF ), are also needed.

Stem cell therapy for the treatment of ED represents a promising potential therapy. More high-level evidence is needed to justify stem cells as a treatment option for ED.

Mesenchymal Stem Cells in the Treatment of Osteoporosis

Osteoporosis is a skeletal disease caused by a variety of reasons, characterized by bone pain and easy fractures, and the majority of patients are elderly. Due to the decline of motor function and nutrient absorption capacity in the elderly, it is difficult to improve the symptoms of osteoporosis. Mesenchymal stem cells (mesenchymal stem cells, MSC) are a group of stem cells that are mainly derived from mesoderm and have self-replication and multiple differentiation potentials. MSCs can not only differentiate into mesenchymal cell lines and other embryonic cell lines, but also have the function of mediating immune regulation in vivo.

disease introduction

Osteoporosis (OP) is a systemic bone metabolic disease characterized by low bone mass and microarchitectural destruction of bone tissue, leading to increased bone fragility and susceptibility to fracture. The disease is common in the elderly, but it can occur at any age. Osteoporosis can be divided into primary and secondary types. Primary osteoporosis refers to other diseases that do not cause the disease; secondary osteoporosis refers to the reduction of bone tissue due to various systemic or endocrine and metabolic diseases.

Mesenchymal stem cells (mesenchymal stem cells, MSC) are a group of stem cells that are mainly derived from mesoderm and have self-replication and multiple differentiation potentials. MSCs can not only differentiate into mesenchymal cell lines and other embryonic cell lines, but also have the function of mediating immune regulation in vivo.

Mesenchymal Stem Cell Therapy for Osteoporosis

A recent study reported that the use of mesenchymal stem cells (MSCs) can effectively treat osteoporosis. The study found that compared with normal mice, bone marrow mesenchymal stem cells (BM-MSCs) in osteoporotic mice were significantly weakened in osteogenic differentiation; after transplantation of BM-MSCs from normal mice, the diseased mice).

Further studies have found that MSCs can treat osteoporosis because normal MSCs can secrete exosomes containing various biologically active components such as nucleic acids, lipids, and proteins to BM-MSCs of diseased mice, which can regulate the activity of other cells. function and activity. The researchers used green fluorescence to label the exosomes secreted by normal MSCs, and red fluorescence to label the bone marrow cells of diseased mice. The results of fluorescence microscopy showed that the former could be effectively absorbed by the latter. After injecting exosomes secreted by normal MSCs into diseased mice, the symptoms of osteoporosis in mice can also be significantly improved.

In addition, the researchers also found that exosomes secreted by normal MSCs contain Fas protein, which can significantly reduce the content of miR-29b in MSCs of diseased mice and increase the activity of intracellular methylases after being absorbed by MSCs of diseased mice , increase the methylation level of Notch promoter and reduce the expression of Notch gene, thereby restoring the function and osteogenic differentiation ability of MSC in diseased mice, and improving the symptoms of osteoporosis in mice.

Osteoporosis can cause bone pain, shortened length, kyphosis, broken bones, and decreased respiratory function. The most common complication is that it is prone to fracture under the action of external force, which seriously affects the patient's health and quality of life. Most of the patients with the disease are the elderly, who are difficult to improve their osteoporosis symptoms due to the decline of motor function and nutrient absorption capacity. This study successfully used MSCs to treat osteoporosis in mice, which provides new ideas and effective therapeutic methods for the treatment of this disease.