Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The potential of platelet-rich plasma injections and stem cell therapy for penile rejuvenation

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.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. 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.

    PubMed  Article  Google Scholar 

  2. 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

    Article  PubMed  Google Scholar 

  3. 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.

    PubMed  Article  Google Scholar 

  4. 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.

    PubMed  Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  6. Turner L, Knoepfler P. Selling stem cells in the USA: assessing the direct-to-consumer industry. Cell Stem Cell. 2016;19:154–7.

    CAS  PubMed  Article  Google Scholar 

  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

    Article  Google Scholar 

  8. 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.

    CAS  PubMed  Article  Google Scholar 

  9. Schlegel PN, Walsh PC. Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function. J Urol. 1987;138:1402–6.

    CAS  PubMed  Article  Google Scholar 

  10. 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.

    CAS  PubMed  Article  Google Scholar 

  11. 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.

    PubMed  Article  Google Scholar 

  12. 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.

    CAS  PubMed  Article  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. 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

    Article  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. 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.

    Google Scholar 

  17. 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.

    PubMed  Article  Google Scholar 

  18. 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.

    PubMed  Article  Google Scholar 

  19. 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

    Article  PubMed  PubMed Central  Google Scholar 

  20. 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

  21. 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

    CAS  Article  PubMed  Google Scholar 

  22. 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/.

  23. 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

  24. 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.

    PubMed Central  Article  CAS  Google Scholar 

  25. 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.

  26. 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.

    Article  Google Scholar 

  27. 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.

    PubMed  PubMed Central  Article  Google Scholar 

  28. 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.

    PubMed  Article  Google Scholar 

  29. Ramasamy R. Safety and efficacy of autologous platelet-rich plasma for erectile dysfunction. In. University of Miami Miller School of Medicine 2021.

  30. 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.

    Google Scholar 

  31. 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.

    CAS  PubMed  Article  Google Scholar 

  32. 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.

    CAS  PubMed  Article  Google Scholar 

  33. 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.

    CAS  PubMed  Article  Google Scholar 

  34. 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.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  35. 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.

    CAS  PubMed  Article  Google Scholar 

  36. 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.

  37. 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.

    PubMed  Article  Google Scholar 

  38. 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.

    CAS  PubMed  Article  Google Scholar 

  39. 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.

    CAS  PubMed  Article  Google Scholar 

  40. 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

    CAS  Article  PubMed  Google Scholar 

  41. 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.

    CAS  PubMed  Article  Google Scholar 

  42. Levine LA, Goldman KE, Greenfield JM. Experience with intraplaque injection of verapamil for Peyronie’s disease. J Urol. 2002;168:621–6.

    CAS  PubMed  Article  Google Scholar 

  43. 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

    CAS  PubMed  Article  Google Scholar 

  44. 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.

    PubMed  Article  Google Scholar 

  45. 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.

    PubMed  Article  Google Scholar 

  46. 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.

    CAS  PubMed  Article  Google Scholar 

  47. 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.

    CAS  PubMed  Article  Google Scholar 

  48. 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

    Article  PubMed  PubMed Central  Google Scholar 

  49. 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.

    Article  Google Scholar 

  50. 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.

    PubMed  Article  Google Scholar 

  51. Somers KD, Dawson DM. Fibrin deposition in Peyronie’s disease plaque. J Urol. 1997;157:311–5.

    CAS  PubMed  Article  Google Scholar 

  52. 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.

    CAS  PubMed  Article  Google Scholar 

  53. 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.

    CAS  PubMed  Article  Google Scholar 

  54. 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.

    CAS  PubMed  Article  Google Scholar 

  55. 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.

    Article  Google Scholar 

  56. 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.

    Article  Google Scholar 

  57. 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.

    CAS  PubMed  Article  Google Scholar 

  58. 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.

    Google Scholar 

  59. Marcovici I. PRP and correction of penile curvature (Peyronie’s disease). Am J Cosmet Surg. 2019;36:117–20.

    Article  Google Scholar 

  60. 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.

  61. Ramasamy R. PRP for treatment of Peyronie’s disease. In. University of Miami Miller, School of Medicine. 2021.

  62. Code of Federal Regulations Title 21, § 1271.15. 2020.

  63. Storrs C. Is platelet-rich plasma an effective healing therapy. Sci Am 2009.

  64. Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, et al. Erectile dysfunction: AUA guideline. J Urol. 2018;200:633–41.

    PubMed  Article  Google Scholar 

  65. 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.

    PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Ranjith Ramasamy.

Ethics declarations

Competing interests

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.

Ethical approval

No ethical approval was required for this review paper that solely analyzed research papers and did not conduct any direct research with human or animal subjects.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41443-021-00482-z

Further reading

Search

Quick links