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.

  • Review Article
  • Published:

Role of regenerative therapies on erectile dysfunction after radical prostatectomy

International Journal of Impotence Research volume 33, pages 488–496 (2021)Cite this article

Subjects

Abstract

The present study provides a review of stem cell therapy as a treatment of erectile dysfunction from peer-reviewed human and animal trials. A literature search was conducted in PubMed-Medline, Scopus, Embase, and Cochrane databases. Tweenty-three animal studies and seven human studies in the period from 1st of January 2000 to 1st of Mai 2020 were included. The seven included human studies are primary phase one trials, and most of them treat erectile dysfunction following radical prostatectomy by injection of stem cells into the corpus cavernosum. The primary outcome measure in all human trials is safety and secondary can stem cells play a role in the recovery of erectile function. All studies conclude that it is safe to use stem cells and the majority of the studies demonstrate an improvement in erectile function. The results from both animal and human trials are promising for stem cells as a restorative treatment, but data from large randomized human phase two trials is missing before it can be concluded, that stem cells is an effective treatment for erectile dysfunction in humans.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The evolutions possibilities of adipose stem cell are shown.

Similar content being viewed by others

References

  1. Campbell JD, Burnett AL. Neuroprotective and nerve regenerative approaches for treatment of erectile dysfunction after cavernous nerve injury. Int J Mol Sci. 2017;18:1794–811.

    Article  PubMed Central  Google Scholar 

  2. Skarecky DW. Robotic-assisted radical prostatectomy after the first decade: surgical evolution or new paradigm. ISRN Urol. 2013;2013:157379.

    PubMed  PubMed Central  Google Scholar 

  3. Kumar A, Tandon S, Samavedi S, Mouraviev V, Bates AS, Patel VR. Current status of various neurovascular bundle-sparing techniques in robot-assisted radical prostatectomy. J Robot Surg. 2016;10:187–200.

    Article  PubMed  Google Scholar 

  4. Haglind E, Carlsson S, Stranne J, Wallerstedt A, Wilderäng U, Thorsteinsdottir T, et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: a prospective, controlled, nonrandomised trial. Eur Urol. 2015;68:216–25.

    Article  PubMed  Google Scholar 

  5. Haahr MK, Azawi NH, Andersen LG, Carlson S, Lund L. A retrospective study of erectile function and use of erectile aids in prostate cancer patients after radical prostatectomy in Denmark. Sex Med. 2017;5:e156–e62.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tal R, Alphs HH, Krebs P, Nelson CJ, Mulhall JP. Erectile function recovery rate after radical prostatectomy: a meta-analysis. J Sex Med. 2009;6:2538–46.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Iacono F, Giannella R, Somma P, Manno G, Fusco F, Mirone V. Histological alterations in cavernous tissue after radical prostatectomy. J Urol. 2005;173:1673–6.

    Article  PubMed  Google Scholar 

  8. Cooperberg MR, Broering JM, Litwin MS, Lubeck DP, Mehta SS, Henning JM, et al. The contemporary management of prostate cancer in the United States: lessons from the cancer of the prostate strategic urologic research endeavor (CapSURE), a national disease registry. J Urol. 2004;171:1393–401.

    Article  PubMed  Google Scholar 

  9. Le JD, Cooperberg MR, Sadetsky N, Hittelman AB, Meng MV, Cowan JE, et al. Changes in specific domains of sexual function and sexual bother after radical prostatectomy. BJU Int. 2010;106:1022–9.

    Article  PubMed  Google Scholar 

  10. Carrier J, Edwards D, Harden J. Men’s perceptions of the impact of the physical consequences of a radical prostatectomy on their quality of life: a qualitative systematic review. JBI Database Syst Rev Implement Rep. 2018;16:892–972.

    Article  Google Scholar 

  11. Bang SL, Almallah YZ. The impact of post-radical prostatectomy urinary incontinence on sexual and orgasmic well-being of patients. Urology. 2016;89:1–5.

    Article  PubMed  Google Scholar 

  12. Hampson LA, Cowan JE, Zhao S, Carroll PR, Cooperberg MR. Impact of age on quality-of-life outcomes after treatment for localized prostate cancer. Eur Urol. 2015;68:480–6.

    Article  PubMed  Google Scholar 

  13. Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N. Engl J Med. 1998;338:1397–404.

    Article  CAS  PubMed  Google Scholar 

  14. Montorsi F, Brock G, Stolzenburg J-U, Mulhall J, Moncada I, Patel HRH, et al. Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled Study (REACTT). Eur Urol. 2014;65:587–96.

    Article  CAS  PubMed  Google Scholar 

  15. Wang X, Wang X, Liu T, He Q, Wang Y, Zhang X. Systematic review and meta-analysis of the use of phosphodiesterase type 5 inhibitors for treatment of erectile dysfunction following bilateral nerve-sparing radical prostatectomy. PLoS ONE. 2014;9:e91327.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Nelson CJ, Scardino PT, Eastham JA, Mulhall JP. Back to baseline: erectile function recovery after radical prostatectomy from the patients’ perspective. J Sex Med. 2013;10:1636–43.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mishra PJ, Banerjee D. Activation and differentiation of mesenchymal stem cells. Methods Mol Biol. 2017;1554:201–9.

    Article  CAS  PubMed  Google Scholar 

  18. Caplan AI. Adult mesenchymal stem cells: when, where, and how. Stem Cells Int. 2015;2015:628767-.

    Article  PubMed  PubMed Central  Google Scholar 

  19. de Resende Izidoro LC, de Almeida Cavalcante Oliveira LM, Bueno Soares G, de Castro Vieira T, de Souza Orlandi F, Polido, et al. Health-related quality of life and psychosocial factors after radical prostatectomy. Acta Paul de Enferm. 2019;32:169–77.

    Google Scholar 

  20. Agochukwu NQ, Wittmann D, Boileau NR, Dunn RL, Montie JE, Kim T, et al. Validity of the patient-reported outcome measurement information system (PROMIS) sexual interest and satisfaction measures in men following radical prostatectomy. J Clin Oncol. 2019;37:JCO1801782–JCO.

    Article  Google Scholar 

  21. Kong EH, Deatrick JA, Bradway CK. Men’s experiences after prostatectomy: a meta-synthesis. Int J Nurs Stud. 2017;74:162–71.

    Article  PubMed  Google Scholar 

  22. Ding D-C, Chang Y-H, Shyu W, Lin S-Z. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transpl. 2015;24:339–47.

    Article  Google Scholar 

  23. Wei X, Yang X, Han Z-P, Qu F-F, Shao L, Shi Y-F. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacologica Sin. 2013;34:747–54.

    Article  CAS  Google Scholar 

  24. Haahr M, Christensen M, Sheikh SP, Lund L. Ugeskr Laeger. 2014;176:V66265.

  25. Reed-Maldonado AB, Lue TF. The current status of stem-cell therapy in erectile dysfunction: a review. World J Mens Health. 2016;34:155–64.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Albersen M, Kendirci M, Van der Aa F, Hellstrom WJG, Lue TF, Spees JL. Multipotent stromal cell therapy for cavernous nerve injury‐induced erectile dysfunction. J Sex Med. 2012;9:385–403.

    Article  CAS  PubMed  Google Scholar 

  27. Bivalacqua TJ, Deng W, Kendirci M, Usta MF, Robinson C, Taylor BK, et al. Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am J Physiol Heart Circ Physiol. 2007;292:H1278–90.

    Article  CAS  PubMed  Google Scholar 

  28. Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;100:1249–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gu X, Thakker PU, Matz EL, Terlecki RP, Marini FC, Allickson JG, et al. Dynamic changes in erectile function and histological architecture after intracorporal injection of human placental stem cells in a pelvic neurovascular injury rat model. J Sex Med. 2020;17:400–11.

    Article  CAS  PubMed  Google Scholar 

  30. Xu Y, Yang Y, Zheng H, Huang C, Zhu X, Zhu Y, et al. Intracavernous injection of size-specific stem cell spheroids for neurogenic erectile dysfunction: efficacy and risk versus single cells. EBioMedicine. 2020;52:102656.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Song L, Zhu J, Zhang X, Cui Z, Fu Q, Huang J, et al. BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury. Int Urol Nephrol. 2016;48:37–45.

    Article  CAS  PubMed  Google Scholar 

  32. You D, Jang MJ, Kim BH, Choi KR, Lee C, Song G, et al. Bone marrow–derived mesenchymal stromal cell therapy in a rat model of cavernous nerve injury: Preclinical study for approval. Cytotherapy. 2016;18:870–80.

    Article  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 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;5:204–10.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 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.

    Article  PubMed  Google Scholar 

  36. Haahr MK, Harken Jensen C, 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;121:203.e6–e13.

    Article  Google Scholar 

  37. 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.

    Article  PubMed  Google Scholar 

  38. Bahk J, Jung JH, Han H, Min S, Lee Y. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant. 2010;8:150–60.

    PubMed  Google Scholar 

  39. 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 

  40. 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.

    Article  PubMed  Google Scholar 

  41. Casiraghi F, Remuzzi G, Abbate M, Perico N. Multipotent mesenchymal stromal cell therapy and risk of malignancies. Stem Cell Rev Rep. 2013;9:65–79.

    Article  CAS  PubMed  Google Scholar 

  42. Kendirci M, Trost L, Bakondi B, Whitney Mandolin J, Hellstrom Wayne JG, Spees Jeffrey L. Transplantation of nonhematopoietic adult bone marrow stem/progenitor cells isolated by p75 nerve growth factor receptor into the penis rescues erectile function in a rat model of cavernous nerve injury. J Urol. 2010;184:1560–6.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Albersen M, Fandel TM, Lin G, Wang G, Banie L, Lin C-S, 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.

    Article  PubMed  Google Scholar 

  44. Piao S, Kim I, Lee J, Hong S, Kim S, Hwang T-K, et al. Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury. J Sexual Med. 2012;9:1968–79.

    Article  CAS  Google Scholar 

  45. Fandel TM, Albersen M, Lin G, Qiu X, Ning H, Banie L, et al. Recruitment of Intracavernously Injected Adipose-Derived Stem Cells to the Major Pelvic Ganglion Improves Erectile Function in a Rat Model of Cavernous Nerve Injury. Eur Urol. 2012;61:201–10.

    Article  PubMed  Google Scholar 

  46. Jeong HH, Piao S, Ha JN, Kim IG, Oh SH, Lee JH, et al. Combined therapeutic effect of udenafil and adipose-derived stem cell (ADSC)/brain-derived neurotrophic factor (BDNF)–membrane system in a rat model of cavernous nerve injury. Urology. 2013;81:1108.e7–e14.

    Article  Google Scholar 

  47. You D, Jang MJ, Lee J, Jeong IG, Kim HS, Moon KH, et al. Periprostatic implantation of human bone marrow-derived mesenchymal stem cells potentiates recovery of erectile function by intracavernosal injection in a rat model of cavernous nerve injury. Urology. 2013;81:104–10.

    Article  PubMed  Google Scholar 

  48. Kim IG, Piao S, Lee JY, Hong SH, Hwang T-K, 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. 2012;19:14–23.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Song K-M, Jin H-R, Park J-M, Choi MJ, Kwon M-H, Kwon K-D, et al. Intracavernous delivery of stromal vascular fraction restores erectile function through production of angiogenic factors in a mouse model of cavernous nerve injury. J Sex Med. 2014;11:1962–73.

    Article  CAS  PubMed  Google Scholar 

  50. Xu Y, Guan R, Lei H, Li H, Wang L, Gao Z, et al. Therapeutic potential of adipose-derived stem cells-based micro-tissues in a rat model of postprostatectomy erectile dysfunction. J Sex Med. 2014;11:2439–48.

    Article  CAS  PubMed  Google Scholar 

  51. Miyamoto K, Inoue S, Kobayashi K, Kajiwara M, Teishima J, Matsubara A. Rat cavernous nerve reconstruction with CD133+ cells derived from human bone marrow. J Sex Med. 2014;11:1148–58.

    Article  CAS  PubMed  Google Scholar 

  52. Bae JH, Shrestha KR, Park YH, Kim IG, Piao S, Jung AR, et al. Comparison between subcutaneous injection of basic fibroblast growth factor-hydrogel and intracavernous injection of adipose-derived stem cells in a rat model of cavernous nerve injury. Urology. 2014;84:1248.e1–7.

    Article  Google Scholar 

  53. Yiou R, Mahrouf-Yorgov M, Trébeau C, Zanaty M, Lecointe C, Souktani R, et al. Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms. Stem Cells. 2016;34:392–404.

    Article  CAS  PubMed  Google Scholar 

  54. Martínez-Salamanca JI, Zurita M, Costa C, Martínez-Salamanca E, Fernández A, Castela A, et al. Dual strategy with oral phosphodiesterase type 5 inhibition and intracavernosal implantation of mesenchymal stem cells is superior to individual approaches in the recovery of erectile and cavernosal functions after cavernous nerve injury in rats. J Sex Med. 2016;13:1–11.

    Article  PubMed  Google Scholar 

  55. Jeon SH, Shrestha KR, Kim RY, Jung AR, Park YH, Kwon O, et al. Combination therapy using human adipose-derived stem cells on the cavernous nerve and low-energy shockwaves on the corpus cavernosum in a rat model of post-prostatectomy erectile dysfunction. Urology. 2016;88:226.e1–.e9.

    Article  Google Scholar 

  56. Nakajima N, Tamaki T, Hirata M, Soeda S, Nitta M, Hoshi A, et al. Purified human skeletal muscle-derived stem cells enhance the repair and regeneration in the damaged urethra. Transplantation. 2017;101:2312–20.

    Article  PubMed  Google Scholar 

  57. Wu H, Tang WH, Zhao LM, Liu DF, Yang YZ, Zhang HT, et al. Nanotechnology-assisted adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury: In vivo cell tracking, optimized injection dosage, and functional evaluation. Asian J Androl. 2018;20:442–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wu Y-N, Chen K-C, Liao C-H, Liu C-L, Chiang H-S. Smooth muscle progenitor cells preserve the erectile function by reducing corporal smooth muscle cell apoptosis after bilateral cavernous nerve crush injury in rats. BioMed Res Int. 2019;2019:8520523.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Jung AR, Park YH, Kim GE, Kim MY, Jeon SH, Kim HY, et al. Stem cell/oxygen-releasing microparticle enhances erectile function in a cavernous nerve injury model. Tissue Engineering Part A. 2020. https://doi.org/10.1089/ten.TEA.2019.0240.

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Odense University Hospital, Odense, Denmark

    S. T. Hansen, M. Lund, L. D. Ostergaard & L. Lund

  2. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    S. T. Hansen, L. D. Ostergaard & L. Lund

Authors
  1. S. T. Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Lund
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. D. Ostergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Lund
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Lund.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

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

Appendix

Appendix

[29, 30, 33, 42, 45, 47, 51,52,53,54, 59].

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hansen, S.T., Lund, M., Ostergaard, L.D. et al. Role of regenerative therapies on erectile dysfunction after radical prostatectomy. Int J Impot Res 33, 488–496 (2021). https://doi.org/10.1038/s41443-020-00406-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41443-020-00406-3

Search

Advanced search

Quick links