Abstract
Penile concerns include erectile dysfunction (ED) and Peyronie disease (PD). Restorative therapies including Stem Cell Therapy (SCT) and Platelet Rich Plasma (PRP) injections are proposed to treat these concerns. SCT encompasses the harvesting and injection of mesenchymal stem cells or stromal vascular fractions from various tissue sources. PRP is derived autologously from a patient’s plasma and is then injected into the penile tissue. These therapies repair damaged penile tissue and promote both new cellular and vascular growth, as demonstrated in basic science studies. Human trials on SCT and PRP for both ED and PD and have yielded promising results with few side effects. While encouraging, small cohort size and lack of blinding or placebo control limit these studies’ external validity. Recently, the first double-blinded randomized controlled trial on PRP for ED was published, providing significant evidence of efficacy. With the rapid commercial availability of SCT and PRP for ED and PD, it is imperative to perform more randomized and placebo-controlled trials with standardized procedures and preparations to evaluate efficacy and safety. This narrative review will summarize the available literature on these penile restorative therapies to date.
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References
Shiri R, Koskimäki J, Tammela TL, Häkkinen J, Auvinen A, Hakama M. Bidirectional relationship between depression and erectile dysfunction. J Urol. 2007;177:669–73.
Kuja-Halkola R, Henningsohn L, D’Onofrio BM, Mills J, Adolfsson A, Larsson H, et al. Mental disorders in Peyronie’s disease: a Swedish cohort study of 3.5 Million Men. J Urol. 2021;205:864–70. https://doi.org/10.1097/JU.0000000000001426
Hou L, Dong Q, Wu Y-J, Sun Y-X, Guo Y-Y, Huo Y-H. Gonadotropins facilitate potential differentiation of human bone marrow mesenchymal stem cells into Leydig cells in vitro. Kaohsiung J Med Sci. 2016;32:1–9.
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.
Matz EL, Pearlman AM, Terlecki RP. Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions. Investig Clin Urol. 2018;59:61–65. https://doi.org/10.4111/icu.2018.59.1.61.
Turner L, Knoepfler P. Selling stem cells in the USA: assessing the direct-to-consumer industry. Cell Stem Cell. 2016;19:154–7.
NIH Consensus Conference. Impotence. NIH consensus development panel on impotence. JAMA. 1993;270:83–90. https://www.ncbi.nlm.nih.gov/pubmed/8510302 Retrieved from
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.
Schlegel PN, Walsh PC. Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function. J Urol. 1987;138:1402–6.
Ayta I, McKinlay J, Krane R. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84:50–56.
Abidu‐Figueiredo M, Ribeiro IC, Chagas MA, Cardoso LE, Costa WS, Sampaio FJ. The penis in diabetes: structural analysis of connective tissue and smooth muscle alterations in a rabbit model. BJU Int. 2011;108:400–4.
Ning H, Lin G, Lue TF, Lin C-S. Neuron-like differentiation of adipose tissue-derived stromal cells and vascular smooth muscle cells. Differentiation. 2006;74:510–8.
Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol-Ren Physiol. 2005;289:F31–F42.
Haahr MK, Jensen CH, Toyserkani NM, Andersen DC, Damkier P, Sørensen JA, 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:e6–203. e13. 203
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 Osteopath Med. 2016;116:e1–e5.
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 Transpl. 2010;8:150–60.
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.
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. https://doi.org/10.1016/j.ebiom.2016.01.024
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. https://doi.org/10.3390/bioengineering6010021
Ory J, Saltzman RG, Blachman-Braun R, Dadoun S, DiFede DL, Premer C, et al. The effect of transendocardial stem cell injection on erectile function in men with cardiomyopathy: results from the TRIDENT, POSEIDON, and TAC-HFT trials. J Sex Med. 2020;17:695–701. https://doi.org/10.1016/j.jsxm.2020.01.003
Cavallo C, Roffi A, Grigolo B, Mariani E, Pratelli L, Merli G, et al. Platelet-rich plasma: The choice of activation method affects the release of bioactive molecules. BioMed Research International [Internet]. 2016;2016:1–7. Available from: https://www.hindawi.com/journals/bmri/2016/6591717/.
Epifanova MV, Chalyi ME, Krasnov AO. Investigation of mechanisms of action of growth factors of autologous platelet-rich plasma used to treat erectile dysfunction. Urologiia. 2017;46–8. https://www.ncbi.nlm.nih.gov/pubmed/28952692
Campbell JD, Burnett AL. Neuroprotective and nerve regenerative approaches for treatment of erectile dysfunction after cavernous nerve injury. Int J Mol Sci. 2017;18:1794.
Chalyj ME, Grigorjan VA, Epifanova MV, Krasnov AO. The effectiveness of intracavernous autologous platelet-rich plasma in the treatment of erectile dysfunction. Urologiia. 2015:76–9. Russian. PMID: 26665770.
Alkhayal S, Lourdes M. PO-01-091 Platelet-rich plasma penile rejuvenation as a treatment for erectile dysfunction: an update. J Sex Med. 2019;16:S71.
Taş T, Çakıroğlu B, Arda E, Onuk Ö, Nuhoğlu B. Early clinical results of the tolerability, safety, and efficacy of autologous platelet-rich plasma administration in erectile dysfunction. Sex Med. 2021;9:100313.
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;18:926–35.
Ramasamy R. Safety and efficacy of autologous platelet-rich plasma for erectile dysfunction. In. University of Miami Miller School of Medicine 2021.
de la Peyronie F. Sur quelques obstacles qui s’ opposent a l’ejaculation naturelle de la semence. Mem Acad R Chir. 1743;1:425–34.
Haag SM, Hauck EW, Szardening-Kirchner C, Diemer T, Cha E-S, Weidner W, et al. Alterations in the transforming growth factor (TGF)-β pathway as a potential factor in the pathogenesis of Peyronie’s disease. Eur Urol. 2007;51:255–61.
Lindsay MB, Schain DM, Grambsch P, Benson RC, Beard CM, Kurland LT. The incidence of Peyronie’s disease in Rochester, Minnesota, 1950 through 1984. J Urol. 1991;146:1007–9.
Braun M, Wassmer G, Klotz T, Reifenrath B, Mathers M, Engelmann U. Epidemiology of erectile dysfunction: results of the ‘Cologne Male Survey’. Int J Impot Res. 2000;12:305–11.
Stuntz M, Perlaky A, des Vignes F, Kyriakides T, Glass D. The prevalence of Peyronie’s disease in the United States: a population-based study. PLoS ONE. 2016;11:e0150157.
Hatfield BS, King CR, Udager AM, Williamson SR, Gandhi JS, Amin MB, et al. Peyronie disease: a clinicopathologic study of 71 cases with emphasis on histopathologic patterns and prevalent metaplastic ossification. Hum Pathol. 2020;104:9–17.
de Jesús MR, Ramasamy R, Ibrahim E, Molina M, Masterson TA 3rd. The use of ultrasonography in the evaluation and management of peyronie’s disease. Urol Video J. 2020;7:100047. https://doi.org/10.1016/j.urolvj.2020.100047. Epub 2020 Jun 15. PMID: 32724898; PMCID: PMC7386432.
Chung E, De Young L, Brock G. Penile traction and Peyronie’s disease: in-vitro analysis of the efficacy of traction on cellular changes in Peyronie’s plaque in a strain culture system. J Sex Med. 2012;9:130–130.
Akkus E, Breza J, Carrier S, Kadioglu A, Rehman J, Lue TE. Is colchicine effective in Peyronie’sdisease? A pilot study. Urology. 1994;44:291–5.
Weidner W, Hauck EW, Schnitker J, Group, P. s. D. S. Potassium paraaminobenzoate (POTABA™) in the treatment of Peyronie’s disease: a prospective, placebo-controlled, randomized study. Eur Urol. 2005;47:530–6.
Smith JF, Shindel AW, Huang YC, Clavijo RI, Flechner L, Breyer BN, et al. Pentoxifylline treatment and penile calcifications in men with Peyronie’s disease. Asian J Androl. 2011;13:322–5. https://doi.org/10.1038/aja.2010.117
Valente EG, Vernet D, Ferrini MG, Qian A, Rajfer J, Gonzalez-Cadavid NF. L-arginine and phosphodiesterase (PDE) inhibitors counteract fibrosis in the Peyronie’s fibrotic plaque and related fibroblast cultures. Nitric Oxide. 2003;9:229–44.
Levine LA, Goldman KE, Greenfield JM. Experience with intraplaque injection of verapamil for Peyronie’s disease. J Urol. 2002;168:621–6.
Wegner HE, Andresen R, Knispel HH, Miller K. Local interferon-alpha 2b is not an effective treatment in early-stage Peyronie’s disease. Eur Urol. 1997;32:190–3. https://www.ncbi.nlm.nih.gov/pubmed/9286652 Retrieved from
Ralph DJ, Raheem AA, Liu G. Treatment of Peyronie’s disease with Collagenase Clostridium histolyticum and vacuum therapy: a randomized, open-label pilot study. J Sex Med. 2017;14:1430–7.
Kim DH, Lesser TF, Aboseif SR. Subjective patient-reported experiences after surgery for Peyronie’s disease: corporeal plication versus plaque incision with vein graft. Urology. 2008;71:698–702.
Wilson SK, Delk JR II. A new treatment for Peyronie’s disease: modeling the penis over an inflatable penile prosthesis. J Urol. 1994;152:1121–3.
Chung E, Van C, Wilson I, Cartmill R. Penile prosthesis implantation for the treatment for male erectile dysfunction: clinical outcomes and lessons learnt after 955 procedures. World J Urol. 2013;31:591–5.
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 https://doi.org/10.1097/GOX.0000000000000622
Epifanova M, Kaprin A, Kostin A, Gvasalia B, Chalyy M, Artemenko S, et al. P-02-29 platelet-rich plasma and shockwave therapy combination for Peyronie’s disease treatment. J Sex Med. 2020;17:S180.
Hatzichristodoulou G, Meisner C, Gschwend JE, Stenzl A, Lahme S. Extracorporeal shock wave therapy in Peyronie’s disease: results of a placebo-controlled, prospective, randomized, single-blind study. J Sex Med. 2013;10:2815–21.
Somers KD, Dawson DM. Fibrin deposition in Peyronie’s disease plaque. J Urol. 1997;157:311–5.
Liu S, Jiang L, Li H, Shi H, Luo H, Zhang Y, et al. Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis. J Investig Dermatol. 2014;134:2648–57.
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;63:551–60.
Gokce A, Abd Elmageed ZY, Lasker GF, Bouljihad M, Kim H, Trost L, et al. Adipose tissue-derived stem cell therapy for prevention and treatment of erectile dysfunction in a rat model of Peyronie’s disease. Andrology. 2014;2:244–51.
Di Mauro M, Russo GI, Della Camera PA, Di Maida F, Cito G, Mondaini N, et al. Extracorporeal shock wave therapy in Peyronie’s disease: clinical efficacy and safety from a single-arm observational study. World J Men’s Health. 2019;37:339–46.
Levy JA, Marchand M, Iorio L, Zribi G, Zahalsky MP. Effects of stem cell treatment in human patients with Peyronie disease. J Osteopath Med. 2015;115:e8–e13.
Okabe K, Yamada Y, Ito K, Kohgo T, Yoshimi R, Ueda M. Injectable soft-tissue augmentation by tissue engineering and regenerative medicine with human mesenchymal stromal cells, platelet-rich plasma and hyaluronic acid scaffolds. Cytotherapy. 2009;11:307–16.
Virag R, Sussman H, Lambion S, de Fourmestraux V. Evaluation of the benefit of using a combination of autologous platelet rich-plasma and hyaluronic acid for the treatment of Peyronie’s disease. Sex Health. 2017;2017:1.
Marcovici I. PRP and correction of penile curvature (Peyronie’s disease). Am J Cosmet Surg. 2019;36:117–20.
Alkandari MH, Touma N, Carrier S. Platelet-Rich Plasma Injections for Erectile Dysfunction and Peyronie’s Disease: A Systematic Review of Evidence. Sex Med Rev. 2021:S2050-0521(21)00003-2. https://doi.org/10.1016/j.sxmr.2020.12.004. Epub ahead of print. PMID: 34219010.
Ramasamy R. PRP for treatment of Peyronie’s disease. In. University of Miami Miller, School of Medicine. 2021.
Code of Federal Regulations Title 21, § 1271.15. 2020.
Storrs C. Is platelet-rich plasma an effective healing therapy. Sci Am 2009.
Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, et al. Erectile dysfunction: AUA guideline. J Urol. 2018;200:633–41.
Nehra A, Alterowitz R, Culkin DJ, Faraday MM, Hakim LS, Heidelbaugh JJ, et al. Peyronie’s disease: AUA guideline. J Urol. 2015;194:745–53.
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We would like to thank Ms. April Mann, director of the University of Miami writing center, for helping us to address grammatical and stylistic elements of our paper through proofreading and feedback.
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JI was responsible for writing the protocol and report, conducting the search, screening potentially eligible studies, extracting and analyzing data, interpreting results, updating reference lists and creating “Summary of findings” tables. SL was responsible for designing the review protocol and screening potentially eligible studies. He contributed to writing the report, providing feedback, extracting and analyzing data, interpreting results, and creating “Summary of findings” tables. IVE contributed to writing the report, screening potentially eligible studies, extracting and analyzing data, and interpreting results. TM provided feedback on the report. RR helped design the review protocol, provided overall guidance, and supplied feedback on the report.
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Thomas Masterson: Isr Endo Pharm Ranjith Ramasamy: Acerus Pharmaceuticals: Consultant Grant Recipient, Boston Scientific: Consultant, Grant Recipient, Coloplast: Grant recipient, Endo Pharmaceuticals: Consultant, grant recipient, Empower Pharmacy: grant recipient, nestle health: consultant, Olympus: grant recipient.
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Israeli, J.M., Lokeshwar, S.D., Efimenko, I.V. et al. The potential of platelet-rich plasma injections and stem cell therapy for penile rejuvenation. Int J Impot Res 34, 375–382 (2022). https://doi.org/10.1038/s41443-021-00482-z
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DOI: https://doi.org/10.1038/s41443-021-00482-z
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