Abstract
The prevalence of erectile dysfunction (ED) has increased in recent decades. Although many treatments offer some benefits for patients with ED, unmet therapeutic needs remain, and promising new approaches are under investigation. One of these approaches is the use of stem-cell (SC) therapy for ED. We comprehensively reviewed the published literature and ongoing phase 1 and phase 2 trials and identified 27 trials by using SC therapy to treat ED. Of the 27 trials, three have been withdrawn, nine have published results, six are complete but without published results, and nine trials are ongoing or have an “unknown” status. Our analysis revealed that SC therapy represents a promising option to treat ED, although published data exist for less than 100 patients. Large placebo-controlled trials with longer follow-up are needed to confirm the long-term safety and efficacy of SC therapy for ED.
Similar content being viewed by others
Introduction
Erectile dysfunction (ED) is a common major sexual disorder among men and can significantly impact quality of life for both patients and their partners with a high incidence and an increasing prevalence worldwide [1, 2]. It is suggested that over 600,000 new cases of ED are expected annually in the USA [3].
The increasing prevalence of ED may result from a concurrent increase in the number of patients with one or more ED risk factors. It has also been shown that the risk for developing ED increases with hypertension, diabetes, heart disease, age, and lower education [3]. Smoking, obesity, depression, psychological causes, and spinal injuries are also risk factors for developing ED [4,5,6]. An increasing number of patients also suffer from postoperative ED following radical prostatectomy despite nerve-sparing surgery [7]. There are many localized conditions related to ED, such as Peyronie’s disease (PD), which is an acquired pathological curvature of the penile shaft due to progressive fibroblastic proliferation of collagenous plaques in the tunica albuginea [8, 9].
The American Urological Association guidelines suggest patients with ED should see a mental health professional as adjunctive therapy [10], which has been shown to improve adherence to treatment plans and enhance the effects of other treatment approaches, resulting in improved erectile function [11]. Other therapeutic options include noninvasive approaches such as lifestyle changes or oral medications, in addition to more invasive treatments such as vacuum constriction devices, intraurethral and intracorporeal injection, and surgically implanted penile prostheses.
Most international clinical guidelines suggest the use of oral phosphodiesterase type 5 inhibitors (PDE5-Is) as first-line therapy for ED because of their excellent efficacy and safety profiles. However, 30–35% of ED patients are not responsive to PDE5-Is [12]. Moreover, PDE5-Is only provide temporary symptom relief and rarely address the underlying etiology of a patient’s ED. Thus, unmet needs in the treatment for ED have prompted the development of novel minimally invasive therapeutic modalities, including stem-cell (SC) therapy.
SC are unique, undifferentiated cells with three essential features: unlimited proliferation, multi-differentiation potency, and perpetual self-renewal. SC also possess unique proangiogenic, antifibrotic, and antiapoptotic characteristics [13] and are subdivided into four main classifications: adult SC (ASC), embryonic SC (ESC), induced pluripotent SC, and amniotic fluid SC [14]. Of these, ASCs are the chief focus of existing research for multiple diseases because of fewer ethical concerns, decreased oncogenic potential, and reduced genetic instability versus other SC groups. ASCs are abundant throughout the body, are able to repair damage and restore function in different tissues [15]. They are named and distinguished by their origin, such as mesenchymal stem cells (MSCs), first described by Friedenstein et al. [16] and hematopoietic stem cells. MSCs have a broad differentiation potential comparable to that of ESCs. Their regenerative capacity has been extensively studied in many conditions, including ED. Initially derived from bone marrow stroma, MSCs have been isolated from a variety of other tissues, such as adipose tissue (ADSC), umbilical cord blood, placenta, umbilical Wharton’s jelly, muscle tissue, fallopian tissue, cartilage, skin, menstrual blood, and urine [17, 18]. MSCs are abundant in nearly all well-vascularized tissues and are related to pericytes, the perivascular cells that wrap around blood capillaries [19]. MSCs were originally thought to restore tissue function through engraftment on to injured host tissue or differentiation into different cell types. However, the recent literature supports the idea that SC exert their regenerative effect by secreting bioactive factors (known as their secretome), which function in a paracrine manner.
Stem-cell therapy for ED: preclinical studies
Bochinski et al. [20] first reported in 2004 the injection of ESC into rat ED models with cavernous nerve injury (CNI). Subsequent studies investigated the effects of SC treatment of ED caused by aging, diabetes, hyperlipidemia, CNI, and other etiologies. The most studied SC cell types in preclinical animal models have been neural crest SC, MSC, ESC, and endothelial progenitor cells.
In 2017, Hou et al. performed a meta-analysis of 20 studies that used a total of 248 rats [21]. The results showed that ADSC therapy can regenerate damaged cavernous tissues. Subgroup analysis also suggested that ADSC modified growth factors such as nerve growth factor, vascular endothelial growth factor, hepatocyte growth factor, and neurotrophic factors such as brain-derived neurotrophic factor, which significantly improved erectile function compared with ADSC alone. Administration of a large number of cells (>1 × 106), insulin therapy combined with ADSC, or hypoxic preconditioning of ADSC resulted in a significant improvement in ED models of diabetic rats.
Several approaches have been used to improve the efficacy of SC treatment of ED. For example, physical administration of hydrogels and biodegradable membranes coated with growth factors also has improved SC therapy in preclinical models [22, 23].
Because of these promising preclinical data, clinical translation of SC therapy for ED has emerged in recent years.
Methods
A literature search on clinical use of SC for ED was conducted
Using PubMed and the United States National Institute of Health database (www.ClinicalTrials.gov) and the European Union Clinical Trials Registry (www.clinicaltrialsregister.eu), the following search terms were used: “erectile dysfunction,” “Peyronie’s disease,” and “stem cell.” We placed an emphasis on SC use in patients with ED, regardless of the cause of ED. For the specific purpose, only phase 1 and 2 clinical trials were analyzed. Exclusion criteria were: (1) non-English literature; (2) duplicated data; (3) preclinical studies, review articles, editorials, comments, and letters.
Results
In PubMed using the terms (“erectile dysfunction”) AND (“stem cell”), 339 articles were identified. Of these, nine articles reporting eight trials were found. One hundred and twenty-nine articles represented preclinical studies, 127 articles were review articles, comments, editorials and letters, and 74 articles were irrelevant for the analysis.
When using the terms (“Peyronie’s disease”) AND (“stem cell”), 49 articles were identified. Of these, two represented clinical trials. Eleven articles described preclinical studies, 31 articles represented review articles, comments, editorials and letters, and 5 articles were irrelevant for the analysis.
Nine clinical trials using SC therapy for ED were identified in PubMed (Table 1).
Safety is the primary endpoint for most studies (eight out of nine), and common sources of SC were adipose tissue, umbilical cord, placenta, or bone marrow. The number of transplanted SC ranged from 1.5 × 107 (15 million) cells to 2 × 109 (2 billion) cells per patient and was reported to be safe without major adverse effects during and/or after treatment.
The secondary endpoint was the efficacy of SC therapy, measured after a single (eight trials) or two consecutive intracavernous injections (one study). All studies described a significant improvement of ED (despite different ED etiologies such as diabetes, PD, or postradical prostatectomy).
Two prospective studies exploring SC therapy for PD were identified. In a 2015 study [24], five patients received placental matrix-derived MSC. No adverse effects were observed. Significant increases in peak systolic velocity (PSV) ranging from 23 cm/s to 42.6 cm/s at 6 weeks, 38.9 cm/s to 49 cm/s at 3 months, and 50.5 cm/s to 67.1 cm/s at 6 months (P < 0.01) were reported. In addition, penile curvature improved, and seven out of ten plaques disappeared at 3 months follow-up.
Lander et al. assessed stromal vascular fraction (SVF) efficacy in patients with PD [25]. SVF is comprised of a mixture of immune modulatory cells, adipose-derived SCs, and endothelial precursor cells, which act synergistically to promote angiogenesis and epithelial cell differentiation. This study examined the effects of combined SVF and shock-wave therapy on Peyronie’s plaque disruption. All 11 PD patients were injected with autologous SVF and received one to six shock-wave treatments. All patients reported subjective improvement in curvature and reduction in plaque size with minimal adverse events. Mean PD questionnaire scores decreased from 15.0 to 8.7, while mean Erectile Hardness Score (EHS) improved from 2.7 to 3.5 over 6 months.
In 2010, Bahk et al. reported the results of a single intracavernous infusion of allogenic human umbilical cord blood stem cells (HUCB-SC) in seven diabetic patients with ED [26]. HUCB-SC (1.5 × 107) were injected into the corpora cavernosa of each patient. Following SC injection, blood flow into the penis, libido, and blood glucose improved without immune suppression. There were no safety concerns during follow-up.
Another phase 1 trial tested the efficacy and safety of placental matrix-derived mesenchymal SC in eight organic ED patients [27]. Three patients reported irritation at the injection site, which disappeared after 2 days, but no other adverse effects were reported. Significant increases in PSV ranging from 25.5 cm/s to 56.5 cm/s at 6 weeks, 32.5 cm/s to 66.7 cm/s at 3 months, and 50.7 cm/s to 73.9 cm/s at 6 months (P < 0.01) were reported.
Yiou et al. [28, 29] conducted a phase 1 and 2 clinical trial (INSTIN: Intro-Cavernous Stem-Cell Injection Clinical Trial) to treat postradical prostatectomy-ED with BM-MNC. This was the first phase 2 human trial to use SC therapy for ED. In the first phase, four escalating doses of autologous BM-MNCs (2 × 107, 2 × 108, 1 × 109, and 2 × 109) were tested in 12 patients with ED refractory to medical therapy. At 6 months, no serious side effects occurred. Intercourse satisfaction (6.8 ± 3.6, 3.9 ± 2.5, P < 0.05) and erectile function (17.2 ± 8.9, 7.3 ± 4.5, P < 0.05) domains of the IIEF-15 as well as erection hardness scale (2.6 ± 1.1, 1.3 ± 0.8, P < 0.05) improved significantly. The clinical benefits correlated with the improvement of PSV, which was sustained at a 1-year follow-up. In phase 2, six additional patients were included and received 1 × 109 BM-MNC. No serious side effects were reported, and erectile function improved. After a mean follow-up of 62.1 ± 11.7 months, erectile function scores appeared lower compared with the 1-year follow-up. The authors discussed that repeated injections might be necessary to prevent a gradual decline in erectile function over time.
In 2018, Haahr et al. [30] revealed the results of a phase 1 clinical trial that included 21 patients with ED following radical prostatectomy. All patients received a single intracavernous injection of autologous adipose-derived regenerative cells freshly isolated after liposuction and were followed for 1 year. Eight reversible minor events were reported because of liposuction and one scrotal and penile hematoma. Eight of 15 patients in the continent group had recovery of erectile function and regained the ability to perform sexual intercourse, IIEF-5 scores were significantly improved at 6 months and 12 months. Incontinent patients reported no significant improvements in erectile function.
Demour et al. conducted an open label, phase 1 clinical trial [31]. Two consecutive intracavernous autologous BM-MSC injections were given at baseline and at 30 days later to treat four diabetic patients with refractory ED. No major adverse effects were reported. The authors found significant improvements of IIEF-15 scores, sexual desire, intercourse satisfaction, EHS, erectile function, and overall satisfaction (P < 0.05 for all comparisons).
In 2019, Protogerou et al. [32] conducted a phase 1 study testing the safety and efficacy of ADMSCs and platelet lysate (PL) for ED. Five men with organic ED received autologous ADMSC suspended in PL, three organic ED patients received PL alone. No severe adverse reactions were reported (except minor pain at the injection site). Both patient groups showed improved IIEF-5 scores at 1 (P < 0.05) and 3 months (P < 0.05). All patients reported increased morning erections and improved penile triplex. No difference was observed between the two groups.
Search in registered trials
Twenty-two trials using the search terms “stem cell” and “erectile dysfunction” were found in the United States National Institute of Health database (www.ClinicalTrials.gov). One trial was excluded (irrelevant for the investigated topic) and three studies were withdrawn. Of the remaining 18 trials, 3 were published (Table 1). Six completed trials lacked publications, five are actively recruiting, one trial is not yet recruiting, and three trials are “unknown.”
Two trials using the search words “stem cell” and “Peyronie’s Disease” were found in the United States National Institute of Health database (www.ClinicalTrials.gov). One was published (Table 1), the other is “unknown.”
One single “ongoing” trial was identified using the search words “stem cell” and “erectile dysfunction” or “Peyronie’s Disease” in the European Union Clinical Trials Registry (www.clinicaltrialsregister.eu).
A total of 15 registered trials without the full results were found (Table 2).
Discussion
When performing a Google search using the terms “erectile dysfunction” and “stem cells,” within 0.48 s, 1,520,000 results appear. Of interest, the majority of these results represent advertising from venders trying to sell unapproved and undifferentiated SC therapies (for the treatment of sexual dysfunction). The social medial content is in large contrast to the actual amount of published data in the scientific literature. Despite a huge public interest in sexual dysfunction and SC therapy, only nine clinical trials using SC therapy for ED in men were published. Collectively, the results show significant improvements in penile hemodynamics and improved erectile function scores. No major adverse effects were described, and SC therapy has shown efficacy in ED of different etiologies.
Most studies (eight trials out of nine) have a 6- or 12-month follow-up. Two studies reported sustained effect at 1 year. Follow-up at longer period (62.1 months) suggested a decline in erectile function over time.
SCs were derived from multiple sources, prepared using various protocols, and administered at various doses. Three published studies did not give the number of cells that were administered.
The specific mechanisms underlying SC efficacy in ED treatment has not been evaluated in clinical studies. Preclinical studies have shown that the differentiation of SCs is not always present during the repair process and the therapeutic effects of SCs can persist regardless of the cell numbers or even after the disappearance of SCs. Cell-free treatments (such as secretomes) have also shown regenerative benefits [13] and are thought to be important for improving erectile functional. The MSC secretomes’ proangiogenic, anti-inflammatory, antiapoptotic, and antifibrotic properties have shown preclinical potential in different animal models of ED and may be a future treatment option for ED [33, 34]. The MSC secretomes hold several advantages over traditional cell-based therapies for regenerative urology such as safety and cost effectiveness [13, 35,36,37,38]. To date, no clinical studies have been published using secretomes to treat ED in men.
Other future treatment options for ED may include injection of platelet-rich plasma, botulinum toxin injection, and low intensity extracorporeal shock-wave therapy [39]. These therapies have shown promising initial results with few side effects. However, these methods are still considered experimental and further investigation is needed. Among all the novel ED treatment options, SC therapy appears to be the most promising. SC may also reverse in part neuronal and structural causes of ED, as shown in preclinical studies [21].
Each study has its own individualized protocol and there are no standardized protocols for SC therapy in the management of ED in general. Therefore, optimization of cellular preparation and development of a standardized method for the general application of SC therapy for ED with regards to the cell type, number, application, and outcome measures is recommended. However, ethical concerns, cost, source, ease of isolation and culture, risks, and effectiveness must be taken into account when selecting the most suitable type of SC protocol [40].
Along with different regulatory and commercial factors to consider, potential SC therapy for ED treatment is becoming increasingly complex. The guidelines put forth by professional societies as well as the FDA for clinical translation of SC therapy should be followed when designing and conducting trials [41, 42].
Conclusions
Preclinical research in animal models has generated excitement for the use of SC as a potentially curative treatment for ED. The primary mechanism proposed is paracrine effects, while possible engraftment and cellular differentiation are potential auxiliary mechanisms. Less than 100 patients have been reported to receive SC injections so far, future large-scale clinical trials with controls are necessary to assess the safety and efficacy of SC therapy for patients with ED. The use of SC in humans continues to be an ethically challenging issue and SC studies must be carefully evaluated. Long-term efficacy and safety of SC therapy for ED treatment need to be evaluated, as the field continues to gain a better understanding of the role regenerative medicine may play in ED management.
References
Nicolosi A, Moreira ED Jr., Shirai M, Bin Mohd Tambi MI, Glasser DB. Epidemiology of erectile dysfunction in four countries: cross-national study of the prevalence and correlates of erectile dysfunction. Urology. 2003;61:201–6.
Korneyev IA, Alexeeva TA, Al-Shukri SH, Bernikov AN, Erkovich AA, Kamalov AA, et al. Prevalence and risk factors for erectile dysfunction and lower urinary tract symptoms in Russian Federation men: analysis from a national population-based multicenter study. Int J Impot Res. 2016;28:74–9.
Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54–61.
Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. A prospective study of risk factors for erectile dysfunction. J Urol. 2006;176:217–21.
Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007;120:151–7.
McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD, et al. Risk factors for sexual dysfunction among women and men: a consensus statement from the fourth international consultation on sexual medicine 2015. J Sex Med. 2016;13:153–67.
Mangir N, Turkeri L. Stem cell therapies in post-prostatectomy erectile dysfunction: a critical review. Can J Urol. 2017;24:8609–19.
Garaffa G, Trost LW, Serefoglu EC, Ralph D, Hellstrom WJ. Understanding the course of Peyronie’s disease. Int J Clin Pract. 2013;67:781–8.
Lopez JA, Jarow JP. Penile vascular evaluation of men with Peyronie’s disease. J Urol. 1993;149:53–5.
Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, et al. Erectile dysfunction: AUA Guideline. J Urol. 2018;200:633–41.
Melnik T, Soares BG, Nasselo AG. The effectiveness of psychological interventions for the treatment of erectile dysfunction: systematic review and meta-analysis, including comparisons to sildenafil treatment, intracavernosal injection, and vacuum devices. J Sex Med. 2008;5:2562–74.
McMahon CN, Smith CJ, Shabsigh R. Treating erectile dysfunction when PDE5 inhibitors fail. BMJ. 2006;332:589–92.
Sun DZ, Abelson B, Babbar P, Damaser MS. Harnessing the mesenchymal stem cell secretome for regenerative urology. Nat Rev Urol. 2019;16:363–75.
Wu J, Izpisua Belmonte JC. Stem cells: a renaissance in human biology research. Cell. 2016;165:1572–85.
Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell. 2004;116:639–48.
Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 1974;17:331–40.
Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell Transplant. 2011;20:5–14.
Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9:641–50.
Caplan AI, New MSC. MSCs as pericytes are sentinels and gatekeepers. J Orthop Res. 2017;35:1151–9.
Bochinski D, Lin GT, Nunes L, Carrion R, Rahman N, Lin CS, et al. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int. 2004;94:904–9.
Hou QL, Ge MY, Zhang CD, Tian DD, Wang LK, Tian HZ, et al. Adipose tissue-derived stem cell therapy for erectile dysfunction in rats: a systematic review and meta-analysis. Int Urol Nephrol. 2017;49:1127–37.
Kim IG, Piao S, Lee JY, Hong SH, Hwang TK, Kim SW, et al. Effect of an adipose-derived stem cell and nerve growth factor-incorporated hydrogel on recovery of erectile function in a rat model of cavernous nerve injury. Tissue Eng Part A. 2013;19:14–23.
Lee SH, Kim IG, Jung AR, Shrestha KR, Lee JH, Park KD, et al. Combined effects of brain-derived neurotrophic factor immobilized poly-lactic-co-glycolic acid membrane with human adipose-derived stem cells and basic fibroblast growth factor hydrogel on recovery of erectile dysfunction. Tissue Eng Part A. 2014;20:2446–54.
Levy JA, Marchand M, Iorio L, Zribi G, Zahalsky MP. Effects of stem cell treatment in human patients with Peyronie disease. J Am Osteopath Assoc. 2015;115:e8–13.
Lander EB, Berman MH, See JR. Stromal vascular fraction combined with shock wave for the treatment of Peyronie’s disease. Plast Reconstr Surg Glob Open. 2016;4:e631.
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;8:150–60.
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:e1–5.
Yiou R, Hamidou L, Birebent B, Bitari D, Le Corvoisier P, Contremoulins I, 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;3:643–5.
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;69:988–91.
Haahr MK, Jensen CH, Toyserkani NM, Andersen DC, Damkier P, Sorensen 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;5:204–10.
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;101:358–65.
Protogerou V, Michalopoulos E, Mallis P, Gontika I, Dimou Z, Liakouras C, et al. Administration of adipose derived mesenchymal stem cells and platelet lysate in erectile dysfunction: a single center pilot study. Bioengineering. 2019;6:21.
Albersen M, Fandel TM, Lin G, Wang G, Banie L, Lin CS, et al. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. J Sex Med. 2010;7:3331–40.
Sun C, Lin H, Yu W, Li X, Chen Y, Qiu X, et al. Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats. Int J Androl. 2012;35:601–7.
Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, et al. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood. 2007;110:1362–9.
Kunter U, Rong S, Boor P, Eitner F, Muller-Newen G, Djuric Z, et al. Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes. J Am Soc Nephrol. 2007;18:1754–64.
Foudah D, Redaelli S, Donzelli E, Bentivegna A, Miloso M, Dalpra L, et al. Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells. Chromosome Res. 2009;17:1025–39.
Jeong JO, Han JW, Kim JM, Cho HJ, Park C, Lee N, et al. Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circ Res. 2011;108:1340–7.
Shauly O, Gould DJ, Patel KM. Emerging nonsurgical and surgical techniques to treat erectile dysfunction: a systematic review of treatment options and published outcomes. J Plast Reconstr Aesthet Surg. 2019;72:532–8.
Gur S, Abdel-Mageed AB, Sikka SC, Hellstrom WJG. Advances in stem cell therapy for erectile dysfunction. Expert Opin Biol Ther. 2018;18:1137–50.
Knoepfler PS. From bench to FDA to bedside: US regulatory trends for new stem cell therapies. Adv Drug Deliv Rev. 2015;82-83:192–6.
Daley GQ, Hyun I, Apperley JF, Barker RA, Benvenisty N, Bredenoord AL, et al. Setting global standards for stem cell research and clinical translation: the 2016 ISSCR guidelines. Stem Cell Rep. 2016;6:787–97.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no financial affiliation or involvement with any organization with a financial interest/conflict associated with the studies discussed in this paper. This includes expert testimony, employment, honoraria, consultancies, stock options or ownership, grants or patents pending/received, or royalties.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
He, M., von Schwarz, E.R. Stem-cell therapy for erectile dysfunction: a review of clinical outcomes. Int J Impot Res 33, 271–277 (2021). https://doi.org/10.1038/s41443-020-0279-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41443-020-0279-8
- Springer Nature Limited