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The use of combination regenerative therapies for erectile dysfunction: rationale and current status


Erectile Dysfunction (ED) is defined as the inability to achieve and maintain an erection sufficient for sexual intercourse. Available treatments for ED provide only symptomatic relief, which is for the most part temporary. Regenerative therapies such as Low Intensity Shockwave, Platelet-Rich Plasma, and Stem Cell therapy can potentially provide a “cure” for ED by reversing the underlying pathology of ED rather than just treating the symptoms. Low Intensity Shockwave therapy is the most evidence based at this point and is thought to act by improving penile blood flow, repairing previous nerve damage, and activating stem cells. Stem Cell therapy takes advantage of the self-replicative potential of stem cells to create new corporal tissue, but also to recruit host cells and angiogenic factors to stimulate endogenous repair. Platelet-Rich Plasma therapy uses concentrated growth factors that already exist within the bloodstream to repair damaged nerves and increase penile blood flow. The use of combination restorative therapy may provide an additive or synergistic benefit greater than any one therapy alone because of its overlapping mechanisms of action on the penis but is a topic that remains to be studied.

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Fig. 1


  1. 1.

    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  Article  Google Scholar 

  2. 2.

    Chung E. A review of current and emerging therapeutic options for erectile dysfunction. Med Sci (Basel). 2019;7:91.

  3. 3.

    Gruenwald I, Appel B, Kitrey ND, Vardi Y. Shockwave treatment of erectile dysfunction. Ther Adv Urol. 2013;5:95–9.

    Article  Google Scholar 

  4. 4.

    Capogrosso P, Frey A, Jensen CFS, Rastrelli G, Russo GI, Torremade J, et al. Low-intensity shock wave therapy in sexual medicine-clinical recommendations from the european society of sexual medicine (ESSM). J Sex Med. 2019;16:1490–505.

    Article  Google Scholar 

  5. 5.

    Gruenwald I, Appel B, Vardi Y. Low-intensity extracorporeal shock wave therapy-a novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy. J Sex Med. 2012;9:259–64.

    Article  Google Scholar 

  6. 6.

    Ding XG, Li SW, Zheng XM, Hu LQ, Hu WL, Luo Y. [Effect of platelet rich plasma on the regeneration of cavernous nerve: experiment with rats]. Zhonghua Yi Xue Za Zhi. 2008;88:2578–80.

    PubMed  Google Scholar 

  7. 7.

    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.

    Article  Google Scholar 

  8. 8.

    Vincent KCS, d’Agostino MC History of Shockwave Treatment and Its Basic Principles.

  9. 9.

    Vardi Y, Appel B, Jacob G, Massarwi O, Gruenwald I. Can low-intensity extracorporeal shockwave therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile dysfunction. Eur Urol. 2010;58:243–8.

    Article  Google Scholar 

  10. 10.

    Burnett AL. Low intensity shock wave therapy in sexual medicine - clinical recommendations from the European Society of Sexual Medicine (ESSM). J Sex Med. 2019;16:1860.

    Article  Google Scholar 

  11. 11.

    Clavijo RI, Kohn TP, Kohn JR, Ramasamy R. Effects of low-intensity extracorporeal shockwave therapy on erectile dysfunction: a systematic review and meta-analysis. J Sex Med. 2017;14:27–35.

    Article  Google Scholar 

  12. 12.

    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;49:822–30.

    CAS  Article  Google Scholar 

  13. 13.

    Feng D, Tang C, Liu S, Yang Y, Han P, Wei W Current management strategy of treating patients with erectile dysfunction after radical prostatectomy: a systematic review and meta-analysis. Int J Impot Res. 2020. (published online).

  14. 14.

    Frey A, Sonksen J, Fode M. Low-intensity extracorporeal shockwave therapy in the treatment of postprostatectomy erectile dysfunction: a pilot study. Scand J Urol 2016;50:123–7.

    Article  Google Scholar 

  15. 15.

    Baccaglini W, Pazeto CL, Correa Barros EA, Timoteo F, Monteiro L, Saad Rached RY, et al. The role of the low-intensity extracorporeal shockwave therapy on penile rehabilitation after radical prostatectomy: a randomized clinical trial. J Sex Med. 2020;17:688–94.

    CAS  Article  Google Scholar 

  16. 16.

    Yee CH, Chan ES, Hou SS, Ng CF. Extracorporeal shockwave therapy in the treatment of erectile dysfunction: a prospective, randomized, double-blinded, placebo controlled study. Int J Urol. 2014;21:1041–5.

    Article  Google Scholar 

  17. 17.

    Fojecki GL, Tiessen S, Osther PJ. Effect of low-energy linear shockwave therapy on erectile dysfunction-a double-blinded, sham-controlled, randomized clinical trial. J Sex Med 2017;14:106–12.

    Article  Google Scholar 

  18. 18.

    American Urological Association. Erectile Dysfunction: AUA Guideline (2018).

  19. 19.

    Sexual Medicine Society of North America. Position Statement: ED Restorative (Regenerative) Therapies.

  20. 20.

    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;9:100343.

    Article  Google Scholar 

  21. 21.

    Filardo G, Kon E, Pereira Ruiz MT, Vaccaro F, Guitaldi R, Di Martino A, et al. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012;20:2082–91.

    Article  Google Scholar 

  22. 22.

    Cameli N, Mariano M, Cordone I, Abril E, Masi S, Foddai ML. Autologous pure platelet-rich plasma dermal injections for facial skin rejuvenation: clinical, instrumental, and flow cytometry assessment. Dermatol Surg. 2017;43:826–35.

    CAS  Article  Google Scholar 

  23. 23.

    Patel AN, Selzman CH, Kumpati GS, McKellar SH, Bull DA. Evaluation of autologous platelet rich plasma for cardiac surgery: outcome analysis of 2000 patients. J Cardiothorac Surg. 2016;11:62.

    Article  Google Scholar 

  24. 24.

    Lee JW, Kwon OH, Kim TK, Cho YK, Choi KY, Chung HY, et al. Platelet-rich plasma: quantitative assessment of growth factor levels and comparative analysis of activated and inactivated groups. Arch Plast Surg. 2013;40:530–5.

    Article  Google Scholar 

  25. 25.

    Campbell JD, Milenkovic U, Usta MF, Albersen M, Bivalacqua TJ. The good, bad, and the ugly of regenerative therapies for erectile dysfunction. Transl Androl Urol. 2020;9:S252–S61.

    Article  Google Scholar 

  26. 26.

    Chen KC, Minor TX, Rahman NU, Ho HC, Nunes L, Lue TF. The additive erectile recovery effect of brain-derived neurotrophic factor combined with vascular endothelial growth factor in a rat model of neurogenic impotence. BJU Int. 2005;95:1077–80.

    CAS  Article  Google Scholar 

  27. 27.

    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;59:61–5.

    Article  Google Scholar 

  28. 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.

    Article  Google Scholar 

  29. 29.

    Epifanova MV, Gvasalia BR, Durashov MA, Artemenko SA. Platelet-rich plasma therapy for male sexual dysfunction: myth or reality? Sex Med Rev. 2020;8:106–13.

    Article  Google Scholar 

  30. 30.

    Safety and efficacy of autologous platelet-rich plasma for erectile dysfunction.

  31. 31.

    Bellio MA, Khan A. Improving cell production techniques to enhance autologous cell therapy. Circ Res 2018;122:191–3.

    CAS  Article  Google Scholar 

  32. 32.

    Strong TD, Gebska MA, Champion HC, Burnett AL, Bivalacqua TJ. Stem and endothelial progenitor cells in erection biology. Int J Impot Res 2008;20:243–54.

    CAS  Article  Google Scholar 

  33. 33.

    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.

    PubMed  Google Scholar 

  34. 34.

    Liu MC, Chang ML, Wang YC, Chen WH, Wu CC, Yeh SD. Revisiting the regenerative therapeutic advances towards erectile dysfunction. Cells. 2020;9:1250.

    CAS  Article  Google Scholar 

  35. 35.

    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.

    CAS  Article  Google Scholar 

  36. 36.

    Ouyang B, Sun X, Han D, Chen S, Yao B, Gao Y, et al. Human urine-derived stem cells alone or genetically-modified with FGF2 Improve type 2 diabetic erectile dysfunction in a rat model. PLoS One. 2014;9:e92825.

    Article  Google Scholar 

  37. 37.

    Haney NM, Gabrielson A, Kohn TP, Hellstrom WJG. The use of stromal vascular fraction in the treatment of male sexual dysfunction: a review of preclinical and clinical studies. Sex Med Rev. 2019;7:313–20.

    Article  Google Scholar 

  38. 38.

    Lokeshwar SD, Patel P, Shah SM, Ramasamy R. A systematic review of human trials using stem cell therapy for erectile dysfunction. Sex Med Rev. 2020;8:122–30.

    Article  Google Scholar 

  39. 39.

    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.

    CAS  Article  Google Scholar 

  40. 40.

    Matz EL, Terlecki R, Zhang Y, Jackson J, Atala A. Stem cell therapy for erectile dysfunction. Sex Med Rev. 2019;7:321–8.

    Article  Google Scholar 

  41. 41.

    Thanh LM, Dam PTM, Nguyen, H-P, Nguyen T-ST, To HM, Nguyen HB, et al. Can Autologous Adipose-Derived Mesenchymal Stem Cell Transplantation Improve Sexual Function in People with Sexual Functional Deficiency?. Stem Cell Rev Rep 2021.

  42. 42.

    Ruffo A, Stanojevic N, Iacono F, Romis L, Romeo G, Di Lauro G. 529 Treating erectile dysfunction with a combination of low-intensity shock waves (LISW) and platelet-rich plasma (PRP) injections. J Sex Med. 2018;15:S318–S9.

    Article  Google Scholar 

  43. 43.

    Ruffo A, Stanojevic N, Romeo G, Riccardo F, Trama F, Iacono F. PS-5-3 management of erectile dysfunction using a combination treatment of low-intensity shock waves (LISW) and platelet rich plasma (PRP) intracavernosal injections. J Sex Med. 2020;17:S133–S4.

    Article  Google Scholar 

  44. 44.

    Zhu GQ, Jeon SH, Bae WJ, Choi SW, Jeong HC, Kim KS, et al. Efficient promotion of autophagy and angiogenesis using mesenchymal stem cell therapy enhanced by the low-energy shock waves in the treatment of erectile dysfunction. Stem Cells Int. 2018;2018:1302672.

    PubMed  PubMed Central  Google Scholar 

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Correspondence to Ranjith Ramasamy.

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Competing interests

RR is a consultant for Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Metuchen, and Nestle Health. All other authors have no conflicts of interest to report.

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Towe, M., Peta, A., Saltzman, R.G. et al. The use of combination regenerative therapies for erectile dysfunction: rationale and current status. Int J Impot Res (2021).

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