Erectile dysfunction is the most common sexual concern men bring to urology, hormone optimization, longevity and regenerative practices. The Massachusetts Male Aging Study reported some degree of erectile dysfunction in 52 percent of men aged 40 to 70 in 1994, the National Institute of Diabetes and Digestive and Kidney Diseases places the US figure between 30 and 50 million men, and Aytaç and colleagues projected the worldwide total to rise from 152 million men in 1995 to 322 million by 2025.
Oral phosphodiesterase-5 inhibitors act on demand by amplifying the nitric oxide signal, and regenerative research studies whether the vessels, nerves and smooth muscle that produce an erection can be supported directly. Three material classes are in that research, platelet-rich plasma injected into the corpora or the tunica, autologous and allogeneic cells including umbilical cord and Wharton's jelly mesenchymal stromal cells, and the extracellular vesicles those cells secrete. This review sets out the physiology each targets, what the randomized trials and meta-analyses report, what the vesicle literature shows in nerve injury and diabetic models, the registered trials, the guideline and regulatory position, and the documentation a practice keeps. It is written for urology, men's health, hormone optimization and regenerative practices and for investigators.
Regulatory position, stated once
PRP prepared at the point of care is a blood component, which 21 CFR 1271.3(d)(2) excludes from the definition of HCT/Ps, and PRP preparation systems reach the US market through 510(k) clearance under product code ORG, whose cleared indication is mixing with bone graft. The FDA states that there are no FDA-approved exosome products, and allogeneic umbilical cord or Wharton's jelly cell products used for treatment generally fall outside the four criteria of 21 CFR 1271.10(a) and follow the biologics pathway. Which material, for which patient and by which route are practitioner decisions this article does not make, and ExaVeyra Sciences supplies exosome material for topical aesthetic use by licensed practitioners and for IND-authorized research.
Erection, sensation and orgasm run on vessels, nerves and smooth muscle working together
Penile erection is a neurovascular event. Sexual stimulation releases nitric oxide from the cavernous nerve terminals and the sinusoidal endothelium, nitric oxide raises cyclic GMP in cavernous smooth muscle, and the relaxed muscle lets arterial blood fill the sinusoids while compressing the subtunical venules against the tunica albuginea, the veno-occlusive mechanism Lue described in his 2000 review in the New England Journal of Medicine.
Sensation, orgasm and desire run on separate wiring. The dorsal nerve of the penis, a branch of the pudendal nerve, carries tactile sensation from the glans; emission and ejaculation are coordinated by sympathetic thoracolumbar outflow and a spinal ejaculation generator; and desire is set centrally by dopaminergic and androgen-dependent circuits. Regenerative research has concentrated on the vascular and nerve levels, which is why most trials measure erectile function and penile blood flow while fewer measure libido, sensitivity or orgasm directly.
| Component | Role in sexual function | What disrupts it | Where regenerative research looks |
|---|---|---|---|
| Sinusoidal endothelium | Releases nitric oxide, regulates inflow | Diabetes, hypertension, smoking, age | Angiogenic signaling (VEGF), endothelial nitric oxide synthase |
| Cavernous nerve | Neuronal nitric oxide (nNOS) that starts erection | Radical prostatectomy, pelvic surgery, diabetic neuropathy | Neurotrophic signaling and nerve regeneration in rat injury models |
| Cavernous smooth muscle | Relaxes to fill sinusoids, maintains veno-occlusion | Fibrosis, apoptosis, TGF-beta1 signaling | Anti-fibrotic and anti-apoptotic cargo of MSCs and their vesicles |
| Tunica albuginea | Fibroelastic envelope that traps blood | Peyronie's plaque, curvature | Anti-fibrotic effects in Peyronie's models and early PRP studies |
| Dorsal and pudendal nerves | Glans sensitivity, afferent input to orgasm | Neuropathy, surgery, age | Secondary endpoints in a minority of trials |
| Central circuits and androgens | Desire, arousal, ejaculatory control | Testosterone deficiency, depression, medications | Hormone optimization and pharmacology, outside the scope of biologics |
Because these components are separate, the endpoint a trial chooses determines what it can show. The International Index of Erectile Function (IIEF) separates erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction into domains, and a study that reports only the erectile function domain says little about libido or orgasm, which is the reason the trials below are described by the domain they actually measured.
PRP for erectile dysfunction now has four placebo-controlled trials and four meta-analyses
The randomized trials
The first double-blind trial was reported by Poulios, Hatzichristou and colleagues in 2021 (NCT04050020). Sixty men aged 40 to 70 with mild or moderate vasculogenic erectile dysfunction received two intracavernosal sessions of PRP or saline a month apart, and the adjusted gain in IIEF erectile function over placebo was 2.7 points at one month, 2.8 at three months and 3.9 at six months (P < .001), with 69 percent of the PRP group reaching the minimal clinically important difference at six months against 27 percent with placebo and no adverse events.
Shaher and colleagues randomized 100 men with mild to moderate erectile dysfunction to three injections of PRP or saline 15 days apart in 2023 and reported the minimal clinically important difference in 70 percent with PRP against 16 percent with saline at six months, with duplex and Sexual Encounter Profile measures also improved and a peak effect at three months. Two trials found the arms similar: Masterson, Ramasamy and colleagues at the University of Miami randomized 61 men in 2023 (NCT04396795) and reported 58.3 against 53.6 percent reaching the clinical threshold at one month, with both arms improving, and Ragheb and colleagues randomized 52 men in 2024 and reported similar IIEF scores between PRP and placebo through six months, with no major adverse events in either study and one minor event per arm in the Miami trial.
What the pooled analyses report
Five systematic reviews published between 2023 and 2026 have organized this literature. Panunzio and colleagues pooled seven controlled studies of 641 men in 2024 and reported a mean IIEF erectile function gain over placebo of 2.99 points at one month, 2.85 at three months and 3.21 at six months. Huang and colleagues pooled 10 studies of 559 men the same year and reported a gain of 3.22 points at six months and a peak systolic velocity increase of 10.32 cm/s against placebo, Falcone and colleagues reported a mean difference of 3.28 points across three randomized trials in 2025, and Zhou and colleagues pooled seven randomized trials of 660 men in 2025 and reported a gain of 2.46 points at 24 weeks, with PRP added to low-intensity shockwave improving IIEF over shockwave alone (P < .0001).
The reviewers rated the certainty low to moderate and named small samples and short follow-up as the main limits, and Poulios and colleagues reported in a 2023 review of 23 preclinical and clinical studies that no major adverse events had been described, with transient pain and bruising the most common effects. The University of Miami COCKTAIL trial (NCT05048667) is testing PRP combined with shockwave against a double sham, and its preliminary meeting report of 56 men has not yet been published in full.
Peyronie's disease and curvature
Peyronie's disease places a fibrous plaque in the tunica albuginea and can cause curvature, pain and loss of rigidity. Schirmann and colleagues reported a fall in curvature from 40.4 to 28.6 degrees after three PRP injections in 17 men in 2022 (P = .007), with IIEF erectile function rising 5 to 7 points, and Chatar and colleagues reported a curvature improvement of about 17 degrees in 65 men, with pain during intercourse falling from 70.7 to 34.25 percent. In a phase 2 randomized crossover trial at the University of Miami, Ledesma and colleagues reported at interim in 2024 that curvature improved to 25 degrees in the arm receiving PRP first (P = .047), with no adverse events, and Asmundo and colleagues reviewed 17 ED and Peyronie's studies of 1,099 patients the same year.
| Study | Design | n | Population | Main endpoint reported | Follow-up |
|---|---|---|---|---|---|
| Poulios 2021 | Double-blind RCT, PRP vs saline | 60 | Mild to moderate vasculogenic ED | IIEF-EF +3.9 vs placebo; MCID 69 vs 27% | 6 months |
| Shaher 2023 | RCT, PRP vs saline | 100 | Mild to moderate ED | MCID 70 vs 16% | 6 months |
| Masterson 2023 | Double-blind RCT, PRP vs saline | 61 | Mild to moderate ED | MCID 58.3 vs 53.6%, both arms improved | 6 months |
| Ragheb 2024 | Double-blind RCT, PRP vs saline | 52 | ED | IIEF similar between arms | 6 months |
| Panunzio 2024 | Meta-analysis | 7 studies, 641 men | Organic ED | IIEF-EF +2.99 to +3.21 vs placebo | 1 to 6 months |
| Huang 2024 | Meta-analysis | 10 studies, 559 men | ED | IIEF-EF +3.22; peak velocity +10.32 cm/s | 6 months |
| Zhou 2025 | Meta-analysis, GRADE | 7 RCTs, 660 men | ED, PRP alone or with shockwave | IIEF +2.46 at 24 weeks | 24 weeks |
| Falcone 2025 | Meta-analysis | 28 studies, 3 RCTs pooled | Vasculogenic ED | IIEF-EF +3.28 vs placebo | Varied |
| Ledesma 2024 | Phase 2 crossover RCT, interim | 28 of 41 | Peyronie's disease | Curvature 25 degrees in PRP-first arm | 6 months |
| Schirmann 2022 | Pilot | 17 | Peyronie's disease | Curvature 40.4 to 28.6 degrees | Per protocol |
Cell studies in erectile dysfunction span cord blood, adipose, bone marrow, placental and Wharton's jelly sources
Wharton's jelly MSCs in diabetic erectile dysfunction
The principal human Wharton's jelly study in men's sexual health was reported by Al Demour, Awidi and colleagues at the University of Jordan in 2021 (NCT02945449). Twenty-two diabetic men received two intracavernous injections of allogeneic Wharton's jelly-derived MSCs, and IIEF-5, the Erection Hardness Score and penile peak systolic velocity improved significantly against baseline at every time point through 12 months, with transient redness and bruising the only adverse effects. A related two-dose study by the same group is registered as NCT03751735 with nine participants completed.
The preclinical work points to a paracrine mechanism. In streptozotocin-diabetic rats, Wharton's jelly MSC transplantation improved intracavernosal pressure in a study published in the Asian Journal of Andrology in 2022, with higher VEGF, endothelial nitric oxide synthase, IGF-1 and basic FGF at the injection site, the same family of signals the Wharton's jelly source guide on this blog describes in the cord secretome.
Bone marrow, adipose, placental and cord blood cells
The first human report came from Bahk and colleagues in 2010, who treated seven diabetic men with umbilical cord blood stem cells and reported the return of morning erections in three within a month. Al Demour and colleagues later gave two injections of autologous bone marrow MSCs to diabetic men, reporting improved IIEF-15 and erectile function domains in a four-man phase 1 study in 2018 and an IIEF-5 rise from 10.4 to 17.9 at six months in eight men in 2024, a gain that had returned toward baseline at 24 months and points to repeat dosing as a design question.
After radical prostatectomy, where cavernous nerve injury drives erectile loss, Yiou and colleagues reported IIEF erectile function rising from 7.3 to 17.4 at six months in 12 men given bone marrow mononuclear cells in a dose-escalation study (NCT01089387). Haahr and colleagues reported recovery of erectile function in 8 of 11 continent men after a single injection of adipose-derived regenerative cells in 2016, with 53 percent of continent men able to have intercourse at 12 months, and the same Odense group's double-blind placebo-controlled trial of 70 men, published by Hansen and colleagues in 2026, found the two arms similar on IIEF-5 at 12 months and on the Erection Hardness Score and RigiScan at six months, without serious adverse events.
Placental cells have entered randomized testing. Levy and colleagues reported improved peak systolic velocity at three and six months after placental-derived cells in 2016, and Ji and colleagues randomized 33 diabetic men in 2025 to placenta-derived MSCs with low-intensity shockwave, cells alone or shockwave alone, reporting IIEF erectile function of 19.8, 17.5 and 16.7 and an Erection Hardness Score above 2 in 70, 45 and 40 percent at six months (P = .045).
What the cell meta-analyses report
Senel and colleagues pooled six clinical studies of 75 men in 2025 and reported a standardized mean IIEF-5 improvement of 1.23 at six months with only minor adverse events, and Helvacı, Burnett and colleagues pooled 11 studies of 140 men in 2026 and reported a positive pooled effect (P < .001) with high heterogeneity, both groups calling for comparative trials. Registered studies continue that work, including a double-blind four-arm trial of allogeneic adipose MSCs after robotic prostatectomy at Houston Methodist (NCT07048314) and a study of a combined protocol with and without Wharton's jelly (NCT04424394).
| Study | Cell source | n | Population | Main endpoint reported | Follow-up |
|---|---|---|---|---|---|
| Al Demour 2021 | Allogeneic Wharton's jelly MSCs | 22 | Diabetic ED | IIEF-5, EHS and peak velocity improved vs baseline | 12 months |
| Al Demour 2024 | Autologous bone marrow MSCs | 8 | Diabetic ED | IIEF-5 10.4 to 17.9 at 6 months | 24 months |
| Ji 2025 | Placenta-derived MSCs with shockwave | 33 | Diabetic ED, randomized 3 arms | IIEF-EF 19.8 vs 17.5 vs 16.7 | 6 months |
| Yiou 2016 | Bone marrow mononuclear cells | 12 | Post-prostatectomy | IIEF-EF 7.3 to 17.4 | 6 months |
| Haahr 2016 | Adipose-derived regenerative cells | 17 | Post-prostatectomy | Recovery in 8 of 11 continent men | 6 months |
| Hansen 2026 | Adipose-derived regenerative cells | 70 | Post-prostatectomy, double-blind RCT | IIEF-5 similar between arms | 12 months |
| Levy 2016 | Placental-derived cells | 8 | ED | Peak systolic velocity improved | 6 months |
| Bahk 2010 | Umbilical cord blood cells | 7 | Diabetic ED | Morning erections returned in 3 | 9 months |
| Senel 2025 | Meta-analysis | 6 studies, 75 men | ED | IIEF-5 SMD 1.23 | 6 months |
Vesicle studies report restored nerve signaling, less smooth muscle loss and less tunical fibrosis in animal models
The cell literature led researchers to ask how much of the effect travels in what cells secrete, and the cavernous nerve injury model has become the main test. Ouyang and colleagues injected MSC-derived exosomes into rats with bilateral cavernous nerve injury in 2018 and reported an intracavernosal to mean arterial pressure ratio of 0.50 against 0.34 with vehicle and 0.65 with whole MSCs, with neuronal nitric oxide synthase nearly doubled and caspase-3 reduced, indicating less smooth muscle apoptosis. Kim and colleagues reported in 2024 that repeated injections of bone marrow MSC exosomes in a crush injury model gave the highest pressure ratio, the most nNOS in the dorsal penile nerve, which carries glans sensitivity, and the highest cGMP in penile tissue.
Vesicle cargo can also be engineered. Liang and colleagues reported in 2021 that exosomes from adipose MSCs overexpressing miR-301a-3p reversed hypoxia-induced erectile dysfunction in rats, improving pressure ratios, smooth muscle content and endothelial nitric oxide synthase through PTEN and TLR4 signaling, an example of the cargo-specific design that the vesicle field is moving toward.
In Peyronie's models, the cell work has focused on the tunica. Castiglione and colleagues reported in European Urology in 2013 that intratunical adipose-derived stem cells prevented fibrosis and improved the pressure ratio from 0.37 to 0.59 in a rat model, and the same group reported in 2019 that stromal vascular fraction prevented the rise in collagen and elastin in the acute phase and that adipose stem cells shifted the collagen III to I ratio to 0.86, against 4.6 in untreated animals, in the chronic phase.
| Study | Model | Material | Reported result |
|---|---|---|---|
| Ouyang 2018 | Rat cavernous nerve injury | MSC exosomes | Pressure ratio 0.50 vs 0.34; nNOS up; apoptosis down |
| Kim 2024 | Rat cavernous nerve crush | Bone marrow MSC exosomes, repeated | Highest pressure ratio; dorsal nerve nNOS and penile cGMP up |
| Liang 2021 | Rat hypoxia model | Engineered adipose MSC exosomes | Pressure ratio, smooth muscle and eNOS improved |
| Wharton's jelly, 2022 | Diabetic rat | Wharton's jelly MSCs | Intracavernosal pressure up; VEGF, eNOS, IGF-1, bFGF up |
| Castiglione 2013 | Rat Peyronie's model | Adipose-derived stem cells | Reported: fibrosis prevented; pressure ratio 0.37 to 0.59 |
| Castiglione 2019 | Rat chronic Peyronie's | Adipose-derived stem cells | Collagen III to I ratio restored |
Human vesicle studies in men's sexual health are at the registration stage, with the trial of exosomes as a complementary treatment for moderate to severe erectile dysfunction listed as NCT07319533, so these models describe mechanisms under investigation. A vesicle product's source cell, isolation method and lot characterization determine which of these studies it can be compared with, which is why the certificate of analysis matters as much in this field as in aesthetics.
Eight registered trials frame the next round of results
| Registry ID | Title (short) | Sponsor | Design | Enrollment | Status, verified October 2026 |
|---|---|---|---|---|---|
| NCT07048314 | Allogeneic adipose MSCs after robotic prostatectomy | Houston Methodist | Phase 1/2, double-blind, 4 arms | 40 planned | Recruiting from July 2026 |
| NCT07319533 | Exosomes as a complementary treatment in moderate to severe ED (the trial's registered title) | Listed on registry | Interventional | Not listed | Title verified |
| NCT05048667 | COCKTAIL: PRP plus shockwave vs double sham | University of Miami | Randomized, double-blind | 60 planned | Preliminary report presented; full publication pending |
| NCT04424394 | Combined protocol with or without Wharton's jelly | BioIntegrate | Phase 1/2, single-blind | 60 planned | Not yet enrolling |
| NCT04396795 | PRP for erectile dysfunction | University of Miami | Phase 2, quadruple-masked RCT | 61 | Completed April 2023; results posted |
| NCT04050020 | PRP for vasculogenic erectile dysfunction | Institute for the Study of Urological Diseases, Greece | Phase 2/3, double-blind RCT | 60 | Completed September 2020; published 2021 |
| NCT03751735 | Two doses of Wharton's jelly MSCs in diabetic ED | University of Jordan investigator | Phase 1/2, open label | 9 | Completed 2019 |
| NCT05147779 | Allogeneic umbilical cord cells for Peyronie's, ED and interstitial cystitis | Foundation for Orthopaedics and Regenerative Medicine | Phase 1, open label | 20 | Terminated after preliminary data |
The evidence base is early and expanding quickly
- PRP now has four placebo-controlled trials of 52 to 100 men, two reporting clear separation from placebo and two reporting improvement in both arms, and the meta-analyses pool to a gain of about 2.5 to 3.3 IIEF erectile function points over placebo.
- Cell studies are mostly small and open label, with the Wharton's jelly study of 22 diabetic men among the larger, and the first double-blind adipose cell trial after prostatectomy found the arms similar at 12 months.
- Durability is under active study, since the bone marrow MSC gains seen at six months had returned toward baseline at 24 months, which has led investigators to study repeat dosing and combination with shockwave.
- Endpoints concentrate on erectile function. Orgasmic function, desire and glans sensitivity are reported as secondary IIEF domains or not at all, so they remain the least studied part of the map.
- Preparations differ by kit, spin, volume and number of sessions, and every result belongs to the preparation that produced it.
- Vesicle data in erectile tissue are preclinical, with the first human study registered.
Guideline societies place these therapies in research protocols, and no product is FDA-approved for a sexual-health indication
The American Urological Association guideline, published by Burnett and colleagues in 2018, describes low-intensity shockwave and intracavernosal stem cell therapy as investigational and PRP as experimental. The European Association of Urology 2024 sexual and reproductive health guideline recommends PRP only within clinical trials and states that stem cell data are insufficient for a clinical recommendation, and the Sexual Medicine Society of North America position statement of 2021 reserves restorative therapies for clinical trials, which is the setting where the registered studies above are generating the next results.
PRP prepared at the point of care is a blood component excluded from the HCT/P definition by 21 CFR 1271.3(d)(2), and its preparation systems are cleared under product code ORG for mixing with bone graft, so an intracavernosal use is a practitioner's off-label decision. The FDA consumer alert current as of April 2024 states that there are no FDA-approved exosome products and lists Wharton's jelly among unapproved products, the December 2019 public safety notification states that exosomes used to treat diseases and conditions are regulated as drugs and biological products, and the agency's August 2025 warning letter to Innate Healthcare Institute cited umbilical cord MSC products marketed for sexual dysfunction.
| Item | US status | Source |
|---|---|---|
| PRP prepared at the point of care | Blood component outside the HCT/P definition | 21 CFR 1271.3(d)(2) |
| PRP preparation systems | 510(k) cleared, Class II; indication is mixing with bone graft | FDA product code ORG |
| Allogeneic umbilical cord or Wharton's jelly cells | Section 361 only if all four 1271.10(a) criteria are met | 21 CFR 1271.10(a) |
| Exosome material | No FDA-approved product for any use | FDA consumer alert, 2024; FDA notification, 2019 |
| Restorative ED therapies | Investigational or experimental; recommended within trials | AUA 2018; EAU 2024; SMSNA 2021 |
Documentation each practice records
- The IIEF or IIEF-5, Erection Hardness Score and Sexual Encounter Profile at baseline and follow-up, with the domains for orgasm and desire recorded separately
- Penile duplex parameters where measured: peak systolic velocity and end-diastolic velocity
- For PRP: kit name, 510(k) number, lot, anticoagulant, centrifuge model, relative centrifugal force and time, volume, injection sites and session interval
- For cells: source tissue, donor screening, manipulation, dose and the regulatory pathway the protocol relies on
- For exosome material: product name, source cell and tissue, lot number, certificate of analysis on file, storage temperature log and time from thaw to application
- Concurrent therapies, including PDE5 inhibitors, shockwave and testosterone, since each changes the reading of an outcome
ExaVeyra Sciences supplies exosome material with the lot number and storage requirements on every order and the certificate of analysis for each lot available on request, so that a practice can file them against the record above. Placebo-controlled trials, pooled analyses and registered vesicle studies are now arriving together in men's sexual health, and the practices that document their preparations carefully will be best placed to read each new result against their own work.
Educational Disclaimer: This article is for educational purposes only and does not constitute medical or legal advice. It reviews published research and registered trials; it does not identify any material, compound, device setting or protocol as safe, effective or appropriate for any patient, and it is not intended to diagnose, treat, cure, or prevent any disease. Conditions named in this article are named as the subjects of the studies cited. Naming a condition studied in a model or a trial does not establish an indication for any product. Exosome material is supplied for topical aesthetic use by licensed practitioners and for laboratory and IND-authorized clinical research. No exosome product is FDA-approved for any use, and ExaVeyra Sciences makes no statement about administration, route, or outcome. Any use of research-grade material in human subjects requires the applicable FDA pathway, such as an investigational new drug application, and institutional review board oversight. Compounded medications are not FDA-approved. They are prepared by a 503A compounding pharmacy licensed by the Texas State Board of Pharmacy for an individual patient against that patient’s prescription, and are available to NPI-verified licensed practitioners only. Discussion of a compound’s literature, including compounds the FDA placed in category 2 of its 503A bulk drug substances policy, is not an offer to supply it. ExaVeyra Sciences is a supplier and takes no part in any diagnosis, treatment decision, study design decision, or plan of care. Findings described are attributed to the peer-reviewed literature, trial registries and agencies cited, and a citation establishes that a question was studied, leaving the suitability of any product for a given patient or protocol to the practitioner’s judgment. The content of these guides is provided for general informational purposes only. It does not constitute legal, medical, or regulatory advice, and does not establish that any particular product or practice is compliant. Regulatory requirements vary by state and depend on the circumstances of each practice. Each practitioner should consult their own legal counsel and the applicable state licensing boards before acting on anything stated here.
References
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- 2.Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49(6):822-830. PMID 9187685.Instrument validation. Carries in this article: the five IIEF domains, erectile function, orgasmic function, desire, intercourse satisfaction and overall satisfaction (pre-2011 landmark).
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- 4.Aytaç IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84:50-56. PMID 10444124.Projection study. Carries in this article: 152 million men in 1995, projected to 322 million by 2025 (pre-2011 landmark).
- 5.National Institute of Diabetes and Digestive and Kidney Diseases. Definition and Facts for Erectile Dysfunction. Last reviewed October 2024. niddk.nih.gov/health-information/urologic-diseases/erectile-dysfunction/definition-facts.Federal health information. Carries in this article: between 30 and 50 million US men with erectile dysfunction; about 40 percent affected at age 40 and 70 percent by age 70.
- 6.Poulios E, Mykoniatis I, Pyrgidis N, Zilotis F, Kapoteli P, Kotsiris D, et al. Platelet-rich plasma (PRP) improves erectile function: a double-blind, randomized, placebo-controlled clinical trial. J Sex Med. 2021;18(5):926-935. PMID 33906807. doi:10.1016/j.jsxm.2021.03.008.Double-blind RCT; n = 60, mild to moderate vasculogenic ED; NCT04050020; 6 months. Carries in this article: IIEF-EF +2.7, +2.8 and +3.9 over placebo at 1, 3 and 6 months; MCID 69 vs 27 percent at 6 months; no adverse events. Disclosure: declared: none; funded by the Institute for the Study of Urological Diseases and the ESSM; the preparation system was supplied by its manufacturer.
- 7.Shaher H, Fathi A, Elbashir S, Abdelbaki SA, Soliman T. Is platelet rich plasma safe and effective in treatment of erectile dysfunction? Randomized controlled study. Urology. 2023;175:114-119. PMID 36736914. doi:10.1016/j.urology.2023.01.028.Placebo-controlled study; n = 100; 3 injections 15 days apart; 6 months. Carries in this article: MCID 70 vs 16 percent at 6 months; duplex and SEP improved; no major side effects.
- 8.Masterson TA, Molina M, Ledesma B, Zucker I, Saltzman R, Ibrahim E, et al. Platelet-rich plasma for the treatment of erectile dysfunction: a prospective, randomized, double-blind, placebo-controlled clinical trial. J Urol. 2023;210(1):154-161. PMID 37120727. PMC10330773. doi:10.1097/JU.0000000000003481.Double-blind RCT; n = 61; NCT04396795; 6 months. Carries in this article: MCID 58.3 vs 53.6 percent at 1 month (P = .730), with IIEF-EF improving in both arms; one minor adverse event per arm.
- 9.Ragheb AM, Lotfy AM, Fahmy M, Elmarakbi AA. Safety and efficacy of platelet-rich plasma injection for treatment of erectile dysfunction: a prospective randomized controlled study. Basic Clin Androl. 2024;34:16. PMID 39375600. doi:10.1186/s12610-024-00232-3.Double-blind RCT; n = 52; 6 months. Carries in this article: IIEF similar between PRP and placebo through 6 months; no adverse events. Disclosure: declared: none.
- 10.Panunzio A, Labate C, Zacheo F, Orlando R, Rizzo FL, Porcaro AB, et al. Platelet-rich plasma intracavernosal injections for the treatment of primary organic erectile dysfunction: a systematic review and meta-analysis of contemporary controlled studies. Int J Impot Res. 2024;36:562-571. PMID 37993601. doi:10.1038/s41443-023-00798-y.Meta-analysis; 7 controlled studies, 641 men. Carries in this article: IIEF-EF +2.99, +2.85 and +3.21 over placebo at 1, 3 and 6 months. Disclosure: declared: none.
- 11.Huang H, Qin J, Wen Z, Liu Y, Chen C, Wang C, et al. Efficacy and safety of platelet-rich plasma (PRP) in erectile dysfunction (ED): a systematic review and meta-analysis. Transl Androl Urol. 2024;13(6):970-982. doi:10.21037/tau-24-30.Meta-analysis; 10 studies, 559 men; PROSPERO CRD42023484693. Carries in this article: IIEF-EF +3.22 at 6 months; peak systolic velocity +10.32 cm/s vs placebo. Disclosure: declared: none.
- 12.Falcone M, Preto M, Keskin H, Solorzano Vazquez JF, Banthia R, Mahendran T, et al. Clinical effects and safety outcomes of platelet-rich plasma therapy in patients with vasculogenic erectile dysfunction: a systematic review and meta-analysis. World J Mens Health. 2025;43. PMID 40263961. doi:10.5534/wjmh.240310.Systematic review of 28 studies, 3 RCTs pooled. Carries in this article: mean difference 3.28 points vs placebo; side effects rare. Disclosure: declared: none.
- 13.Zhou Z, Wang Y, Chai Y, Wang T, Yan P, Zhang Y, et al. The efficacy of platelet-rich plasma (PRP) alone or in combination with low intensity shock wave therapy (Li-SWT) in treating erectile dysfunction: a systematic review and meta-analysis of seven randomized controlled trials. Aging Male. 2025;28(1):2472786. PMID 40037837. doi:10.1080/13685538.2025.2472786.Meta-analysis of 7 RCTs, 660 men, GRADE. Carries in this article: IIEF +1.97 at 12 weeks and +2.46 at 24 weeks; PRP plus shockwave over shockwave alone (P < .0001).
- 14.Poulios E, Mykoniatis I, Pyrgidis N, Kalyvianakis D, Hatzichristou D. Platelet-rich plasma for the treatment of erectile dysfunction: a systematic review of preclinical and clinical studies. Sex Med Rev. 2023;11(4):359-368. doi:10.1093/sxmrev/qead027.Systematic review; 23 studies. Carries in this article: no major adverse events reported; transient pain and bruising.
- 15.Saltzman RG, Molina ML, Ledesma BR, Ibrahim E, Masterson TA, Ramasamy R. Rationale and design for the COCKTAIL trial: a single-center, randomized, double-blind, sham-controlled study combining shockwave therapy and platelet-rich plasma for erectile dysfunction. Eur Urol Focus. 2023;9(1). PMID 36280578. doi:10.1016/j.euf.2022.09.015.Trial protocol; NCT05048667. Carries in this article: the design of the double-sham combination trial. Disclosure: NIH/NIDDK R01DK130991.
- 16.Schirmann A, Boutin E, Faix A, Yiou R. Tolerance and efficacy of platelet-rich plasma injections in Peyronie's disease: pilot study. Prog Urol. 2022;32(12):856-861. PMID 35778315. doi:10.1016/j.purol.2022.05.004.Pilot; n = 17; 3 injections. Carries in this article: curvature 40.4 to 28.6 degrees (P = .007); IIEF-EF up 5 to 7 points; no side effects.
- 17.Chatar A, Ammani A, El Anzaoui J. Platelet-rich plasma in patients affected with Peyronie's disease. Arab J Urol. 2023;21(2):69-75. PMID 37234679. doi:10.1080/2090598X.2022.2135284.Prospective series; n = 65. Carries in this article: curvature improved about 17 degrees (P < .001); pain during intercourse 70.7 to 34.25 percent.
- 18.Ledesma BR, Velasquez DA, Egemba C, Molina M, Ibrahim E, Costantini-Mesquita F, et al. A phase 2 randomized, placebo-controlled crossover trial to evaluate safety and efficacy of platelet-rich plasma injections for Peyronie's disease: clinical trial update. Int J Impot Res. 2024;36(8):813-817. PMID 38424354. doi:10.1038/s41443-024-00844-3.Crossover RCT; 41 randomized, 28 at interim. Carries in this article: curvature 25 degrees in the PRP-first arm at 6 months (P = .047); no adverse events. Disclosure: NIH and ACS funding; declared: none.
- 19.Asmundo MG, Durukan E, von Rohden E, Thy SA, Jensen CFS, Fode M. Platelet-rich plasma therapy in erectile dysfunction and Peyronie's disease: a systematic review of the literature. World J Urol. 2024;42(1):359. PMID 38811395. doi:10.1007/s00345-024-05065-3.Systematic review; 17 studies, 1,099 patients. Carries in this article: Peyronie's cohorts reported mean curvature reductions of about 16 to 24 degrees, with the review noting that controlled data remain limited.
- 20.Al Demour S, Adwan S, Jafar H, Rahmeh R, Alhawari H, Awidi A. Safety and efficacy of 2 intracavernous injections of allogeneic Wharton's jelly-derived mesenchymal stem cells in diabetic patients with erectile dysfunction: phase 1/2 clinical trial. Urol Int. 2021;105(11-12):935-943. PMID 34384079. doi:10.1159/000517364.Uncontrolled phase 1/2; n = 22 diabetic men; NCT02945449; 12 months. Carries in this article: IIEF-5, EHS and peak systolic velocity improved vs baseline at every time point; transient redness and bruising only.
- 21.Human umbilical cord Wharton's jelly-derived mesenchymal stem cell transplantation could improve diabetic intracavernosal pressure. Asian J Androl. 2022;24(2):171-175. PMID 33975986.Animal study, streptozotocin-diabetic rats, 4 weeks. Carries in this article: improved intracavernosal pressure with higher VEGF, eNOS, IGF-1 and bFGF at the injection site.
- 22.Bahk JY, Jung JH, Han H, Min SK, Lee YS. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant. 2010;8(2):150-160. PMID 20565373.Case series; the study treated 7 men, with 3 controls. Carries in this article: morning erections returned in 3 men within a month (pre-2011 landmark).
- 23.Al Demour S, Jafar H, Adwan S, AlSharif A, Alhawari H, Alrabadi A, et al. Safety and potential therapeutic effect of two intracavernous autologous bone marrow derived mesenchymal stem cells injections in diabetic patients with erectile dysfunction: an open label phase I clinical trial. Urol Int. 2018;101(3):358-365. PMID 30173210. doi:10.1159/000492120.Phase 1; n = 4; NCT02945462; 12 months. Carries in this article: IIEF-15 (P = .04) and erectile function domain (P = .03) improved; well tolerated.
- 24.Al Demour S, Adwan S, Jafar H, et al. Stem cell therapy in diabetic men with erectile dysfunction: a 24-month follow-up of safety and efficacy of two intracavernous autologous bone marrow derived mesenchymal stem cells injections, an open label phase 2 clinical trial. Basic Clin Androl. 2024;34:13. PMID 38965462. doi:10.1186/s12610-024-00229-y.Phase 2; n = 8 analyzed; 24 months. Carries in this article: IIEF-5 10.4 to 17.9 at 6 months, 10.6 at 24 months; minor adverse events only. Disclosure: University of Jordan grant; declared: none.
- 25.Yiou R, Hamidou L, Birebent B, Bitari D, Lecorvoisier P, Contremoulins I, et al. Safety of intracavernous bone marrow-mononuclear cells for postradical prostatectomy erectile dysfunction: an open dose-escalation pilot study. Eur Urol. 2016 (published online 2015). doi:10.1016/j.eururo.2015.09.026.Phase 1/2; n = 12, 4 dose groups; NCT01089387; 6 months. Carries in this article: IIEF-EF 7.3 to 17.4 (P = .006); EHS 1.3 to 2.6; no serious side effects.
- 26.Yiou R, Hamidou L, Birebent B, et al. Intracavernous injections of bone marrow mononucleated cells for postradical prostatectomy erectile dysfunction: final results of the INSTIN clinical trial. Eur Urol Focus. 2017;3(6):643-645. doi:10.1016/j.euf.2017.06.009.Final report of the INSTIN trial. Carries in this article: completion of the bone marrow mononuclear cell program after prostatectomy.
- 27.Haahr MK, Jensen CH, Toyserkani NM, Andersen DC, Damkier P, Sørensen JA, et al. Safety and potential effect of a single intracavernous injection of autologous adipose-derived regenerative cells in patients with erectile dysfunction following radical prostatectomy: an open-label phase I clinical trial. EBioMedicine. 2016;5:204-210. PMID 27077129. doi:10.1016/j.ebiom.2016.01.024.Phase 1; n = 17; NCT02240823; 6 months. Carries in this article: recovery in 8 of 11 continent men; median IIEF-5 7 to 17 (P = .0069). Disclosure: the cell-processing system was supplied by its manufacturer.
- 28.Haahr MK, Harken Jensen C, Toyserkani NM, et al. A 12-month follow-up after a single intracavernous injection of autologous adipose-derived regenerative cells in patients with erectile dysfunction following radical prostatectomy: an open-label phase I clinical trial. Urology. 2018;121:203.e6-203.e13. PMID 29958973.Follow-up; n = 21; 12 months. Carries in this article: 8 of 15 continent men (53 percent) able to have intercourse; no serious adverse events.
- 29.Hansen ST, Andersen DC, Jensen CH, Damkier P, Sørensen JA, Lund L. A randomized double-blind, placebo-controlled trial of adipose-derived regenerative cells injected into corpora cavernosum following radical prostatectomy. Eur Urol Focus. 2026. PMID 41760422.Double-blind RCT; n = 70; 12 months. Carries in this article: IIEF-5, EHS and RigiScan similar between arms; no serious adverse events.
- 30.Levy JA, Marchand M, Iorio L, Cassini W, Zahalsky MP. Determining the feasibility of managing erectile dysfunction in humans with placental-derived stem cells. J Am Osteopath Assoc. 2016;116(1):e1-e5. doi:10.7556/jaoa.2016.007.Open-label; n = 8; NCT02398370; 6 months. Carries in this article: peak systolic velocity improved at 3 and 6 months; IIEF change not significant; injection-site irritation in 3.
- 31.Ji YH, Zhang YF, Tan X, Hou HZ, Yao Z, Zhang B. High-activity placenta-derived mesenchymal stem cells combined with low-intensity extracorporeal shock wave therapy for diabetic erectile dysfunction: a prospective randomized controlled trial. Stem Cell Res Ther. 2025;16(1):359. PMID 40629484. doi:10.1186/s13287-025-04499-9.RCT, 3 arms; n = 33; ChiCTR2200059271; 6 months. Carries in this article: IIEF-EF 19.8 vs 17.5 vs 16.7; EHS above 2 in 70, 45 and 40 percent (P = .045). Disclosure: national and institutional grants; declared: none.
- 32.Senel S, Sevinc AH, Gultekin H, Ravshanbekovich AJ, Besiroglu H, Dursun M, et al. Stem cell therapy for erectile dysfunction: promise or reality? A systematic review and meta-analysis of clinical trials. BMC Urol. 2025;25:222. doi:10.1186/s12894-025-01913-5.Meta-analysis; 11 studies, 6 pooled, 75 men. Carries in this article: IIEF-5 SMD 1.23 at 6 months; minor adverse events only. Disclosure: declared: none.
- 33.Helvacı G, Bilgin A, Burnett AL, Sezen SF. Stem cell therapy for erectile dysfunction: a systematic review and meta-analysis. Transl Androl Urol. 2026;15(7):243. PMID 42582616. doi:10.21037/tau-2026-0348.Meta-analysis; 11 studies, 140 men. Carries in this article: positive pooled IIEF effect (P < .001) with high heterogeneity. Disclosure: one author reports device-industry fellowship support and stock in a sexual medicine company.
- 34.Ouyang X, Han X, Chen Z, Fang J, Huang X, Wei H. MSC-derived exosomes ameliorate erectile dysfunction by alleviation of corpus cavernosum smooth muscle apoptosis in a rat model of cavernous nerve injury. Stem Cell Res Ther. 2018;9:246. doi:10.1186/s13287-018-1003-1.Correction: Stem Cell Res Ther. 2022;13:508. Animal study; n = 8 per group. Carries in this article: pressure ratio 0.50 vs 0.34 with vehicle; nNOS 0.33 vs 0.18; caspase-3 reduced.
- 35.Kim MY, Jo MS, Choi SG, Moon HW, Park J, Lee JY. Repeated injections of mesenchymal stem cell-derived exosomes ameliorate erectile dysfunction in a cavernous nerve injury rat model. World J Mens Health. 2024;42(4):787-796. doi:10.5534/wjmh.230218.Animal study; crush injury. Carries in this article: repeated dosing gave the highest pressure ratio, dorsal penile nerve nNOS and penile tissue cGMP. Disclosure: national research grant; declared: none.
- 36.Liang L, Zheng D, Lu C, et al. Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models. Stem Cell Res Ther. 2021;12:87. doi:10.1186/s13287-021-02161-8.Animal study. Carries in this article: engineered vesicle cargo improved pressure ratio, smooth muscle and eNOS via PTEN and TLR4. Disclosure: declared: none.
- 37.Castiglione F, Hedlund P, Van der Aa F, Bivalacqua TJ, Rigatti P, Van Poppel H, et al. Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie's disease. Eur Urol. 2013. PMID 23040209. doi:10.1016/j.eururo.2012.09.034.Animal study; 27 rats. Carries in this article: the study reported fibrosis prevented; pressure ratio 0.37 to 0.59 (P = .03).
- 38.Castiglione F, Hedlund P, Weyne E, Hakim L, Montorsi F, Salonia A, et al. Intratunical injection of stromal vascular fraction prevents fibrosis in a rat model of Peyronie's disease. BJU Int. 2019;124(2):342-348. PMID 30267556. doi:10.1111/bju.14570.Animal study; 24 rats, acute phase. Carries in this article: the study reported that SVF improved erectile function and prevented the rise in collagen and elastin.
- 39.Castiglione F, Hedlund P, Weyne E, et al. Intratunical injection of human adipose tissue-derived stem cells restores collagen III/I ratio in a rat model of chronic Peyronie's disease. Sex Med. 2019;7(1):93-103. doi:10.1016/j.esxm.2018.09.003.Animal study; 27 rats, chronic phase. Carries in this article: collagen III to I ratio 0.86 vs 4.6 untreated; erectile pressures similar.
- 40.Houston Methodist. Allogeneic adipose-derived MSCs after robotic prostatectomy. ClinicalTrials.gov NCT07048314. clinicaltrials.gov/study/NCT07048314.Phase 1/2, double-blind, 4 arms; 40 planned. Status: recruiting from July 2026.
- 41.Exosomes as a complementary treatment in severe to moderate erectile dysfunction. ClinicalTrials.gov NCT07319533. clinicaltrials.gov/study/NCT07319533.Registered interventional study. Status: title verified October 2026.
- 42.University of Miami. COCKTAIL: shockwave therapy and platelet-rich plasma for erectile dysfunction. ClinicalTrials.gov NCT05048667. clinicaltrials.gov/study/NCT05048667.Randomized, double-blind, sham-controlled; 60 planned. Status: preliminary report presented at AUA 2024; full publication pending.
- 43.BioIntegrate. DualStim with or without Wharton's jelly. ClinicalTrials.gov NCT04424394. clinicaltrials.gov/study/NCT04424394.Phase 1/2, single-blind; 60 planned. Status: not yet enrolling.
- 44.University of Miami. Platelet-rich plasma for the treatment of erectile dysfunction. ClinicalTrials.gov NCT04396795. clinicaltrials.gov/study/NCT04396795.Phase 2, quadruple-masked; 61 enrolled. Status: completed April 2023; results posted January 2024.
- 45.Institute for the Study of Urological Diseases, Greece. Platelet-rich plasma for vasculogenic erectile dysfunction. ClinicalTrials.gov NCT04050020. clinicaltrials.gov/study/NCT04050020.Phase 2/3, double-blind; 60 enrolled. Status: completed September 2020; published as entry 6.
- 46.Al-Adwan S (University of Jordan). Efficacy of Wharton's jelly in erectile dysfunction, two doses in diabetic men. ClinicalTrials.gov NCT03751735. clinicaltrials.gov/study/NCT03751735.Phase 1/2, open label; 9 enrolled. Status: completed 2019.
- 47.Foundation for Orthopaedics and Regenerative Medicine. Allogeneic umbilical cord stem cells for Peyronie's disease, erectile dysfunction and interstitial cystitis. ClinicalTrials.gov NCT05147779. clinicaltrials.gov/study/NCT05147779.Phase 1, open label; 20 enrolled. Status: terminated after preliminary data.
- 48.Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, et al. Erectile dysfunction: AUA guideline. J Urol. 2018;200(3):633-641. PMID 29746858. doi:10.1016/j.juro.2018.05.004.Clinical practice guideline. Carries in this article: shockwave and intracavernosal stem cell therapy described as investigational and PRP as experimental (statements 23 to 25).
- 49.European Association of Urology. EAU Guidelines on Sexual and Reproductive Health, 2024 edition. uroweb.org/guidelines/sexual-and-reproductive-health.Clinical practice guideline. Carries in this article: PRP for ED within clinical trials; stem cell data insufficient for a recommendation; intralesional PRP for Peyronie's not to be used outside clinical trials.
- 50.Liu JL, Chu KY, Gabrielson AT, Wang R, Trost L, Broderick G, et al. Restorative therapies for erectile dysfunction: position statement from the Sexual Medicine Society of North America (SMSNA). Sex Med. 2021;9(3):100343. PMID 34000480. doi:10.1016/j.esxm.2021.100343.Society position statement. Carries in this article: restorative therapies reserved for clinical trials.
- 51.U.S. Food and Drug Administration. Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. Content current as of April 2024. fda.gov/vaccines-blood-biologics/consumers-biologics/consumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomes.Carries in this article: no FDA-approved exosome products; Wharton's jelly listed among unapproved products.
- 52.U.S. Food and Drug Administration. Public Safety Notification on Exosome Products. December 6, 2019. fda.gov/vaccines-blood-biologics/safety-availability-biologics/public-safety-notification-exosome-products.Carries in this article: exosomes used to treat diseases and conditions in humans are regulated as drugs and biological products.
- 53.U.S. Food and Drug Administration. Warning letter to Innate Healthcare Institute, August 15, 2025. fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters.Carries in this article: umbilical cord MSC products marketed for sexual dysfunction cited by the agency.
- 54.U.S. Food and Drug Administration. 21 CFR 1271.3(d), definition of HCT/Ps, including paragraph (d)(2), which excludes whole blood, blood components and blood derivative products. ecfr.gov/current/title-21/section-1271.3.Federal regulation. Carries in this article: PRP is a blood component outside the HCT/P definition.
- 55.U.S. Food and Drug Administration. 21 CFR 1271.10(a), criteria for regulation solely under section 361 of the PHS Act. ecfr.gov/current/title-21/section-1271.10.Federal regulation. Carries in this article: the four criteria that cell products must meet.
- 56.U.S. Food and Drug Administration. Product Classification database, product code ORG: platelet and plasma separator for bone graft handling; 21 CFR 864.9245, Class II, 510(k). accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?id=ORG.Carries in this article: the cleared indication of PRP preparation systems.