Autologous mesenchymal stem cell therapy for diabetic men with erectile dysfunction. Is it promising? A pilot study


Submitted: August 23, 2023
Accepted: September 7, 2023
Published: November 21, 2023
Abstract Views: 584
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Purpose: to assess safety and efficacy of autologous mesenchymal bone marrow stem cell injection in penile cavernosal tissue for erectile dysfunction therapy in diabetic men. Methods: The subjects of this study were diabetic men suffering erectile dysfunction, non-responding to maximum dose of oral PDE5I. Mesenchymal bone marrow stem cells were aspirated and injected after preparation in both corpora cavernosa at 3, 9 o’clock position. Erectile function was assessed by the International Index of Erectile Function and penile Doppler study, before and after 6 months after injection. Results: 4 patients out of 10 achieve hard erection adequate for satisfactory coitus, and 2 patients achieved penile hardness with addition of pharmacological therapy with sildenafil 100mg. Peak systolic velocity increased significantly in 4 patients (2 arteriogenic and 2 mixed erectile dysfunction), from 12∼22 cm/s to 32∼69 cm/s. Variations in end-diastolic velocity increased substantially in 2 patients with venogenic insufficiency alone at follow-up from 4∼5 cm /s to -4∼-3 cm/s. Conclusions: Despite promising stem cell treatment efficacy for patients with erectile dysfunction, more clinical studies and researches are still warranted.


Aytaç IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999; 84:50-6. DOI: https://doi.org/10.1046/j.1464-410x.1999.00142.x

Lue FT, Erectile dysfunction N Engl J Med., 2000; 342:1802-13. DOI: https://doi.org/10.1056/NEJM200006153422407

Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994; 151:54-61. DOI: https://doi.org/10.1016/S0022-5347(17)34871-1

Ponholzer A, Temml C, Mock K, et al. Prevalence and risk factors for erectile dysfunction in 2869 men using a validated questionnaire. Eur Urol. 2005; 47:80-5. DOI: https://doi.org/10.1016/j.eururo.2004.08.017

Penson DF, Latini DM, Lubeck DP, et al. Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database. Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients? Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database. Diabetes Care. 2003; 26:1093-9. DOI: https://doi.org/10.2337/diacare.26.4.1093

Cameron NE, Cotter MA. Erectile dysfunction and diabetes mellitus: mechanistic considerations from studies in experimental models. Curr Diabetes Rev. 2007; 3:149-58. DOI: https://doi.org/10.2174/157339907781368977

Vickers MA, Satyanarayana R. Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus. Int J Impot Res 2002; 14:466-71. DOI: https://doi.org/10.1038/sj.ijir.3900910

Kolluru GK, Bir SC, Kevil CG. Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med. 2012; 2012:918267. DOI: https://doi.org/10.1155/2012/918267

McCullough AR, Barada JH, Fawzy A, et al. Achieving treatment optimization with sildenafil citrate (Viagra) in patients with erectile dysfunction. Urology. 2002; 60 (Suppl 2):28-38. DOI: https://doi.org/10.1016/S0090-4295(02)01688-6

Carvalheira AA, Pereira NM, Maroco J, Forjaz V. Dropout in the treatment of erectile dysfunction with PDE5: a study on predictors and a qualitative analysis of reasons for discontinuation. J Sex Med. 2012; 9:2361-9. DOI: https://doi.org/10.1111/j.1743-6109.2012.02787.x

Nishimatsu H, Suzuki E, Kumano S, et al. Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration of erectile function in diabetic rats. J Sex Med. 2012; 9:482-93. DOI: https://doi.org/10.1111/j.1743-6109.2011.02469.x

Ouyang B, Sun X, Han D, 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; 9:92825. DOI: https://doi.org/10.1371/journal.pone.0092825

Qiu X, Lin H, Wang Y, et al. Intracavernous transplantation of bone marrow derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats. J Sex Med 2011; 8:427-36. DOI: https://doi.org/10.1111/j.1743-6109.2010.02118.x

Lin CS, Xin Z, Dai J, et al. Stem-cell therapy for erectile dysfunction. Expert Opin Biol Ther. 2013; 13:1585-97. DOI: https://doi.org/10.1517/14712598.2013.847085

Albersen M, Lin G, Fandel TM, et al. Functional, metabolic, and morphologic characteristics of a novel rat model of type 2 diabetesassociated erectile dysfunction. Urology. 2011; 78:476.e1-8. DOI: https://doi.org/10.1016/j.urology.2011.03.024

Dashwood MR, Crump A, Shi-Wen X, Loesch A. Identification of neuronal nitric oxide synthase (nNOS) in human penis: a potential role of reduced neuronally-derived nitric oxide in erectile dysfunction. Curr Pharm Biotechnol. 2011; 12:1316-21. DOI: https://doi.org/10.2174/138920111798280965

Zhou F, Xin H, Liu T, et al. Effects of icariside II on improving erectile function in rats with streptozotocin-induced diabetes. J Androl. 2012; 33:832-44. DOI: https://doi.org/10.2164/jandrol.111.015172

Cellek S, Foxwell NA, Moncada S. Two phases of nitrergic neuropathy in streptozotocin-induced diabetic rats. Diabetes. 2003; 52:2353-62. DOI: https://doi.org/10.2337/diabetes.52.9.2353

Qiu X, Lin G, Xin Z, et al. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med. 2013; 10:738-46. DOI: https://doi.org/10.1111/jsm.12024

Costa C, Soares R, Castela A, et al. Increased endothelial apoptotic cell density in human diabetic erectile tissue-comparison with clinical data. J Sex Med. 2009; 6:826-35. DOI: https://doi.org/10.1111/j.1743-6109.2008.01110.x

Liang X, Ding Y, Zhang Y, et al. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant. 2014; 23:1045-1059. DOI: https://doi.org/10.3727/096368913X667709

Yiou R, Hamidou L, Birebent B, 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. DOI: https://doi.org/10.1016/j.eururo.2015.09.026

Haahr MK, Jensen CH, Toyserkani NM, et al. Safety and potential effect of a single intracavernous injection of autologous adiposederived regenerative cells in patients with erectile dysfunction following radical prostatectomy: an open-label phase I clinical trial. EBioMedicine 2016; 5:204-10. DOI: https://doi.org/10.1016/j.ebiom.2016.01.024

Bahk JY, Jung JH, Han H, et al. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant. 2010; 8:150-60.

Casiraghi F, Remuzzi G, Abbate M, Perico N. Multipotent mesenchymal stromal cell therapy and risk of malignancies. Stem Cell Rev. 2013; 9:65-79. DOI: https://doi.org/10.1007/s12015-011-9345-4

Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008; 8:726-36. DOI: https://doi.org/10.1038/nri2395

Qiu X, Villalta J, Ferretti L, et al. Effects of intravenous injection of adipose-derived stem cells in a rat model of radiation therapyinduced erectile dysfunction. J Sex Med. 2012; 9:1834-41. DOI: https://doi.org/10.1111/j.1743-6109.2012.02753.x

Alwaal A, Hussein AA, Lin CS, Lue TF. Prospects of stem cell treatment in benign urological diseases. Korean J Urol. 2015; 56:257-65. DOI: https://doi.org/10.4111/kju.2015.56.4.257

Choi WY, Jeon HG, Chung Y, et al. Isolation and characterization of novel, highly proliferative human CD34/CD73-double-positive testis-derived stem cells for cell therapy. Stem Cells Dev. 2013; 22:2158-73. DOI: https://doi.org/10.1089/scd.2012.0385

You D, Jang MJ, Lee J, 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. DOI: https://doi.org/10.1016/j.urology.2012.08.046

Soebadi MA, Moris L, Castiglione F, et al. Advances in stem cell research for the treatment of male sexual dysfunctions. Curr Opin Urol. 2016; 26:129-39. DOI: https://doi.org/10.1097/MOU.0000000000000255

Levy J, Marchand M, Iorio L, et al. Determining the feasibility of managing erectile dysfunction in humans with placental-derived stem cells. J Am Osteopath Assoc. 2016; 116:e1-e5. DOI: https://doi.org/10.7556/jaoa.2016.007

Alhefnawy, M. A., Salah, E., Bakry, S., Khalifa, T. M., Rafaat, A., Hammad, R., Sobhy, A., & Wahsh, A. (2023). Autologous mesenchymal stem cell therapy for diabetic men with erectile dysfunction. Is it promising? A pilot study. Archivio Italiano Di Urologia E Andrologia, 95(4). https://doi.org/10.4081/aiua.2023.11669

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