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Mesenchymal stem cell therapy improves erectile dysfunction in experimental spinal cord injury

International Journal of Impotence Research volume 32, pages 308–316 (2020)Cite this article

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Abstract

The aim of this study is to investigate the therapeutic potential of adipose-derived mesenchymal stem cell (AD-MSC) from brown adipose tissue on erectile dysfunction (ED) in experimentally induced spinal cord injury in rats. 24 male Wistar rats were divided into 3 groups; control, spinal cord injury (SCI) + vehicle, and SCI + AD-MSC. To induce SCI, a standard weight-drop method that induced a moderate to severe injury (100 g/cm force) at T7-T10, was used. AD-MSC (3 × 105 cells /5 μL) was applied by local transplantation into the region of injury. At the end of four-weeks, rats underwent neurological examinations and then intracavernosal and mean arterial pressures (ICP and MAP) measurements. After decapitation, spinal cord and cavernosal tissue samples were taken to analyze neuronal nitric oxide synthase (n-NOS), proto-oncogene protein c-FOS and nerve growth factor (NGF). Tissues were also examined histologically. Spinal cord injury caused decrease on NGF and n-NOS levels while c-FOS was increased. The ICP/MAP value in vehicle-treated SCI rats was found to be significantly higher than the control group. On the other hand, in SCI + AD-MSC group, all these parameters were reversed back to control levels. AD-MSC therapy may be beneficial against erectile dysfunction in experimentally induced SCI by ameliorating neuronal damage.

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References

  1. Li X, Yang C, Li L, Xiong J, Xie L, Yang B, et al. A therapeutic strategy for spinal cord defect: human dental follicle cells combined with aligned PCL/PLGA electrospun material. Biomed Res Int. 2015;2015:197183.

    PubMed  PubMed Central  Google Scholar 

  2. Soler JM, Previnaire JG, Denys P, Chartier-Kastler E. Phosphodiesterase inhibitors in the treatment of erectile dysfunction in spinal cord-injured men. Spinal Cord. 2007;45:169–73.

    Article  CAS  Google Scholar 

  3. Tavukcu HH, Sener TE, Tinay I, Akbal C, Ersahin M, Cevik O, et al. Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats. Clin Exp Pharm Physiol. 2014;41:309–16.

    Article  CAS  Google Scholar 

  4. Lin G, Banie L, Ning H, Bella AJ, Lin CS, Lue TF. Potential of adipose-derived stem cells for treatment of erectile dysfunction. J Sex Med. 2009;6(Suppl 3):320–7.

    Article  Google Scholar 

  5. Krampera M, Marconi S, Pasini A, Galie M, Rigotti G, Mosna F, et al. Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus. Bone 2007;40:382–90.

    Article  CAS  Google Scholar 

  6. Xu P, Yang X. The efficacy and safety of mesenchymal stem cell transplantation for spinal cord injury patients: a meta-analysis and systematic review. Cell Transpl. 2019;28:36–46.

    Article  Google Scholar 

  7. Yalvac ME, Yilmaz A, Mercan D, Aydin S, Dogan A, Arslan A, et al. Differentiation and neuro-protective properties of immortalized human tooth germ stem cells. Neurochem Res. 2011;36:2227–35.

    Article  CAS  Google Scholar 

  8. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  CAS  Google Scholar 

  9. Mangir N, Akbal C, Tarcan T, Simsek F, Turkeri L. Mesenchymal stem cell therapy in treatment of erectile dysfunction: autologous or allogeneic cell sources? Int J Urol. 2014;21:1280–5.

    Article  Google Scholar 

  10. Karaoz E, Aksoy A, Ayhan S, Sariboyaci AE, Kaymaz F, Kasap M. Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol. 2009;132:533–46.

    Article  CAS  Google Scholar 

  11. Aras Y, Sabanci PA, Kabatas S, Duruksu G, Subasi C, Erguven M, et al. The effects of adipose tissue-derived mesenchymal stem cell transplantation during the acute and subacute phases following spinal cord injury. Turk Neurosurg. 2016;26:127–39.

    PubMed  Google Scholar 

  12. Martínez-Salamanca JI, Zurita M, Costa C, 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  Google Scholar 

  13. Yang J, Zhang Y, Zang G, Wang T, Yu Z, Wang S, et al. Adipose-derived stem cells improve erectile function partially through the secretion of IGF-1, bFGF, and VEGF in aged rats. Andrology 2018;6:498–509.

    Article  CAS  Google Scholar 

  14. Zhou F, Hui Y, Xin H, Xu YD, Lei HE, Yang BC, et al. Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats. Asian J Androl. 2017;19:91–97.

    Article  CAS  Google Scholar 

  15. Milenkovic U, Albersen M, Castiglione F. The mechanisms and potential of stem cell therapy for penile fibrosis. Nat Rev Urol. 2019;16:79–97.

    Article  Google Scholar 

  16. Allen AR. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column: a preliminary report. JAMA. 1911;57:878–80.

    Article  Google Scholar 

  17. Gale K, Kerasidis H, Wrathall JR. Spinal cord contusion in the rat: behavioral analysis of functional neurologic impairment. Exp Neurol. 1985;88:123–34.

    Article  CAS  Google Scholar 

  18. Mullerad M, Donohue JF, Li PS, Scardino PT, Mulhall JP. Functional sequelae of cavernous nerve injury in the rat: is there model dependency. J Sex Med. 2006;3:77–83.

    Article  Google Scholar 

  19. Sener TE, Tavukcu HH, Atasoy BM, Cevik O, Kaya OT, Cetinel S, et al. Resveratrol treatment may preserve the erectile function after radiotherapy by restoring antioxidant defence mechanisms, SIRT1 and NOS protein expressions. Int J Impot Res. 2018;30:179–88.

    Article  CAS  Google Scholar 

  20. Singh A, Tetreault L, Kalsi-Ryan S, Nouri A, Fehlings MG. Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol. 2014;6:309–31.

    PubMed  PubMed Central  Google Scholar 

  21. DeBrot A, Yao L. The combination of induced pluripotent stem cells and bioscaffolds holds promise for spinal cord regeneration. Neural Regen Res. 2018;13:1677–84.

    Article  Google Scholar 

  22. Amemori T, Ruzicka J, Romanyuk N, Jhanwar-Uniyal M, Sykova E, Jendelova P. Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats. Stem Cell Res Ther. 2015;6:257.

    Article  Google Scholar 

  23. Toksoz S, Erdem SR, Peskircioglu CL, Keskin U. The effect of long-term oral tadalafil treatment on corpus cavernosum function in an experimental spinal cord transection rat model. Spinal Cord. 2013;51:663–7.

    Article  CAS  Google Scholar 

  24. Kim YW, Park SY, Kim JY, Huh JY, Jeon WS, Yoon CJ, et al. Metformin restores the penile expression of nitric oxide synthase in high-fat-fed obese rats. J Androl. 2007;28:555–60.

    Article  CAS  Google Scholar 

  25. Bucan V, Vaslaitis D, Peck CT, Strauss S, Vogt PM, Radtke C. Effect of exosomes from rat adipose-derived mesenchymal stem cells on neurite outgrowth and sciatic nerve regeneration after crush injury. Mol Neurobiol. 2019;56:1812–24.

    Article  CAS  Google Scholar 

  26. Bao CS, Li XL, Liu L, Wang B, Yang FB, Chen LG. Transplantation of human umbilical cord mesenchymal stem cells promotes functional recovery after spinal cord injury by blocking the expression of IL-7. Eur Rev Med Pharm Sci. 2018;22:6436–47.

    Google Scholar 

  27. Pan F, Zhang J, Liu Y, Lu L, Qiu X, Lv K, et al. Intracavernosal pressure recording to evaluate erectile function in rodents. J Vis Exp. 2018;136:e56798.

  28. Temeltas G, Dagci T, Evren V, Lekili M. Effects of neuronal and glial restricted precursor cells transplantation on erectile function after experimentally induced spinal cord injury. J Sex Med. 2009;6:3265–73.

    Article  Google Scholar 

  29. Mnich K, Carleton L, Kavanagh E, Doyle K, Samali A, Gorman A. Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner. Cell Death Dis. 2014;5:e1202.

    Article  CAS  Google Scholar 

  30. Fiore M, Chaldakov GN, Aloe L. Nerve growth factor as a signaling molecule for nerve cells and also for the neuroendocrine-immune systems. Rev Neurosci. 2009;20:133–45.

    Article  CAS  Google Scholar 

  31. Liu Y, Li Q, Zhang B, Ban DX, Feng SQ. Multifunctional biomimetic spinal cord: New approach to repair spinal cord injuries. World J Exp Med. 2017;7:78–83.

    Article  Google Scholar 

  32. Wang L, Zhao Y, Liu Y, Akiyama K, Chen C, Qu C, et al. IFN-gamma and TNF-alpha synergistically induce mesenchymal stem cell impairment and tumorigenesis via NFkappaB signaling. Stem Cells. 2013;31:1383–95.

    Article  CAS  Google Scholar 

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Funding

This study was supported by Marmara University Scientific Research Projects Committee with the grant number SAG-C-YLP-070317-0094.

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Authors and Affiliations

  1. Marmara University, School of Pharmacy, Department of Pharmacology, Istanbul, Turkey

    Ömercan Albayrak, Büşra Ertaş & Göksel Şener

  2. Marmara University, School of Medicine, Department of Urology, Istanbul, Turkey

    Tarık Emre Şener

  3. Istanbul Medeniyet University, School of Medicine, Department of Neurosurgery, Istanbul, Turkey

    Mehmet Erşahin

  4. Marmara University, School of Pharmacy, Department of Biotechnology, Istanbul, Turkey

    Suna Özbaş-Turan & Ceyda Ekentok

  5. Haydarpaşa Sultan Abdulhamid Han Research and Training Hospital, Department of Urology, Istanbul, Turkey

    Hasan Hüseyin Tavukçu

  6. Adnan Menderes University, School of Medicine, Department of Biochemistry, Aydın, Turkey

    Özge Çevik

  7. Marmara University, School of Medicine, Department of Histology & Embryology, Istanbul, Turkey

    Şule Çetinel

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  1. Ömercan Albayrak
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  2. Tarık Emre Şener
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  6. Hasan Hüseyin Tavukçu
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  9. Büşra Ertaş
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Correspondence to Göksel Şener.

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Albayrak, Ö., Şener, T., Erşahin, M. et al. Mesenchymal stem cell therapy improves erectile dysfunction in experimental spinal cord injury. Int J Impot Res 32, 308–316 (2020). https://doi.org/10.1038/s41443-019-0168-1

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  • DOI: https://doi.org/10.1038/s41443-019-0168-1

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