Advertisement

Erectile Dysfunctions

  • Seyed Mohammad Kazem AghamirEmail author
  • Fateme Guitynavard
Chapter
  • 22 Downloads

Abstract

So far, many basic studies addressing the concept of stem cell therapy for ED. The stem cells mechanism of action is to induce angiogenesis and so increase the cavernosal smooth muscle cells within corporal bodies. Generally, erectile dysfunction treatment focuses on the symptomatic reprieve and, thus, aims to provide a temporary relief rather than cure or reverse the cause. The large number of difficult-to-treat patients has motivated the researchers to look for new treatment approaches that instead of offering ad hoc symptomatic care focus on the cure and restoration of the underlying cause. Regenerative medicine has evolved widely over the past few decades and the effects of growth factor therapy, gene transfer, stem cells, and tissue engineering to restore erectile function have been demonstrated in preclinical trials.

With the subject of administration of stem cells in animal models of erectile dysfunction due to aging, type 1 and type 2 diabetes, cavernous nerve injury, Peyronie disease, and even penile trauma, a number of preclinical studies have been published. Based on these studies, there is a general consensus among researchers that using mesenchymal stem cells -mainly from the bone marrow and adipose tissue- would be a promising approach for treatment of ED.

Human umbilical cord blood stem cells have recently demonstrated beneficial effects on erectile function when administered into the penises of men with severe type 2 diabetes. This influence, however, has been short-lived and not lasting. In an open dose-escalation study, another Phase I trial investigated the intracavenous administration of bone marrow cells following radical prostatectomy and reported no serious adverse effects.

Conclusions on the efficacy of these trials should be drawn with the caution as these trials are designed to test safety (no control group); however, preliminary efficacy results were encouraging, with improvement in erectile function and penile vascularization measurements in a small set of patients. Although these preliminary safety data are promising, there is an eager anticipation for larger Phase I – III studies and practical tests.

This chapter discusses the current status and future outlook of stem cell therapy for erectile dysfunction treatment.

Keywords

Erectile dysfunction Treatment Stem cell 

Notes

Acknowledgments

Special thanks to Dr. Mostafa Esmaeili and Maryam Farahani.

References

  1. 1.
    Hellstrom WJ, Gittelman M, Karlin G, Segerson T, Thibonnier M, Taylor T, et al. Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. Urology. 2003;61(4):8–14.PubMedCrossRefGoogle Scholar
  2. 2.
    Wrishko R, Sorsaburu S, Wong D, Strawbridge A, McGill J. Safety, efficacy, and pharmacokinetic overview of low-dose daily administration of tadalafil. J Sex Med. 2009;6(7):2039–48.PubMedCrossRefGoogle Scholar
  3. 3.
    Hatzichristou DG, Apostolidis A, Tzortzis V, Ioannides E, Yannakoyorgos K, Kalinderis A. Sildenafil versus intracavernous injection therapy: efficacy and preference in patients on intracavernous injection for more than 1 year. J Urol. 2000;164(4):1197–200.PubMedCrossRefGoogle Scholar
  4. 4.
    Mulcahy JJ, Wilson SK. Current use of penile implants in erectile dysfunction. Curr Urol Rep. 2006;7(6):485–9.PubMedCrossRefGoogle Scholar
  5. 5.
    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(10):2439–48.PubMedCrossRefGoogle Scholar
  6. 6.
    He Y, He W, Qin G, Luo J, Xiao M. Transplantation KCNMA 1 modified bone marrow-mesenchymal stem cell therapy for diabetes mellitus-induced erectile dysfunction. Andrologia. 2014;46(5):479–86.PubMedCrossRefGoogle 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(6):904–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Gou X, He W-Y, Xiao M-Z, Qiu M, Wang M, Deng Y-Z, et al. Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats. Asian J Androl. 2011;13(2):332.PubMedCrossRefGoogle Scholar
  9. 9.
    Kendirci M, Trost L, Bakondi B, Whitney MJ, Hellstrom WJ, Spees JL. 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(4):1560–6.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Albersen M, Fandel TM, Lin G, Wang G, Banie L, Lin CS, 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(10):3331–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Yamzon JL, Kokorowski P, Koh CJ. Stem cells and tissue engineering applications of the genitourinary tract. Pediatr Res. 2008;63(5):472.PubMedCrossRefGoogle Scholar
  12. 12.
    Kemp KC, Hows J, Donaldson C. Bone marrow-derived mesenchymal stem cells. Leuk Lymphoma. 2005;46(11):1531–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Vernet D, Nolazco G, Cantini L, Magee TR, Qian A, Rajfer J, et al. Evidence that osteogenic progenitor cells in the human tunica albuginea may originate from stem cells: implications for peyronie disease. Biol Reprod. 2005;73(6):1199–210.PubMedCrossRefGoogle Scholar
  14. 14.
    Nolazco G, Kovanecz I, Vernet D, Gelfand RA, Tsao J, Ferrini MG, et al. Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat. BJU Int. 2008;101(9):1156–64.PubMedCrossRefGoogle Scholar
  15. 15.
    Lin G, Alwaal A, Zhang X, Wang J, Wang L, Li H, et al. Presence of stem/progenitor cells in the rat penis. Stem Cells Dev. 2014;24(2):264–70.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109(5):625–37.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 2004;10(1):64.PubMedCrossRefGoogle Scholar
  18. 18.
    Kim SH, Kwon CH, Nakano I. Detoxification of oxidative stress in glioma stem cells: mechanism, clinical relevance, and therapeutic development. J Neurosci Res. 2014;92(11):1419–24.PubMedCrossRefGoogle Scholar
  19. 19.
    Smart N, Riley PR. The stem cell movement. Circ Res. 2008;102(10):1155–68.PubMedCrossRefGoogle Scholar
  20. 20.
    Leri A, Rota M, Hosoda T, Goichberg P, Anversa P. Cardiac stem cell niches. Stem Cell Res. 2014;13(3):631–46.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Moore KA, Lemischka IR. Stem cells and their niches. Science. 2006;311(5769):1880–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Crisan M, Yap S, Casteilla L, Chen C-W, Corselli M, Park TS, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3(3):301–13.PubMedCrossRefGoogle Scholar
  23. 23.
    Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 2013;502(7473):637.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466(7308):829.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118(2):149–61.CrossRefGoogle Scholar
  26. 26.
    Chow A, Lucas D, Hidalgo A, Méndez-Ferrer S, Hashimoto D, Scheiermann C, et al. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med. 2011;208(2):261–71.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B, Helwani F, et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood. 2010;116(23):4815–28.CrossRefGoogle Scholar
  28. 28.
    Katayama Y, Battista M, Kao W-M, Hidalgo A, Peired AJ, Thomas SA, et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell. 2006;124(2):407–21.PubMedCrossRefGoogle Scholar
  29. 29.
    Coskun S, Chao H, Vasavada H, Heydari K, Gonzales N, Zhou X, et al. Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells. Cell Rep 9: 581–590 Dege C, Hagman J (2014) Mi-2/NuRD chromatin remodeling complexes regulate B and T-lymphocyte development and function. Immunol Rev. 2014;261:126–40.CrossRefGoogle Scholar
  30. 30.
    Broxmeyer HE. Chemokines in hematopoiesis. Curr Opin Hematol. 2008;15(1):49–58.PubMedCrossRefGoogle Scholar
  31. 31.
    Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441(7097):1075.PubMedCrossRefGoogle Scholar
  32. 32.
    Galli R, Borello U, Gritti A, Minasi MG, Bjornson C, Coletta M, et al. Skeletal myogenic potential of human and mouse neural stem cells. Nat Neurosci. 2000;3(10):986.PubMedCrossRefGoogle Scholar
  33. 33.
    Zhao L-R, Duan W-M, Reyes M, Keene CD, Verfaillie CM, Low WC. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol. 2002;174(1):11–20.PubMedCrossRefGoogle Scholar
  34. 34.
    Lutolf MP, Blau HM. Artificial stem cell niches. Adv Mater. 2009;21(32–33):3255–68.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Beerman I, Rossi DJ. Epigenetic regulation of hematopoietic stem cell aging. Exp Cell Res. 2014;329(2):192–9.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Zhao M, Perry JM, Marshall H, Venkatraman A, Qian P, He XC, et al. Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells. Nat Med. 2014;20(11):1321.PubMedCrossRefGoogle Scholar
  37. 37.
    Meletis K, Wirta V, Hede S-M, Nistér M, Lundeberg J, Frisén J. p53 suppresses the self-renewal of adult neural stem cells. Development. 2006;133(2):363–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Liu Y, Elf SE, Miyata Y, Sashida G, Liu Y, Huang G, et al. p53 regulates hematopoietic stem cell quiescence. Cell Stem Cell. 2009;4(1):37–48.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell. 2007;128(2):325–39.PubMedCrossRefGoogle Scholar
  40. 40.
    Renault VM, Rafalski VA, Morgan AA, Salih DA, Brett JO, Webb AE, et al. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell. 2009;5(5):527–39.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, et al. Regulation of the HIF-1α level is essential for hematopoietic stem cells. Cell Stem Cell. 2010;7(3):391–402.PubMedCrossRefGoogle Scholar
  42. 42.
    Horsley V, Aliprantis AO, Polak L, Glimcher LH, Fuchs E. NFATc1 balances quiescence and proliferation of skin stem cells. Cell. 2008;132(2):299–310.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Goldstein J, Fletcher S, Roth E, Wu C, Chun A, Horsley V. Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation. Genes Dev. 2014;28(9):983–94.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Hatzfeld J, Li M-L, Brown EL, Sookdeo H, Levesque J-P, O’Toole T, et al. Release of early human hematopoietic progenitors from quiescence by antisense transforming growth factor beta 1 or Rb oligonucleotides. J Exp Med. 1991;174(4):925–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Kandasamy M, Lehner B, Kraus S, Sander PR, Marschallinger J, Rivera FJ, et al. TGF-beta signalling in the adult neurogenic niche promotes stem cell quiescence as well as generation of new neurons. J Cell Mol Med. 2014;18(7):1444–59.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Schmid B, Furthauer M, Connors SA, Trout J, Thisse B, Thisse C, et al. Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation. Development. 2000;127(5):957–67.PubMedGoogle Scholar
  47. 47.
    Zhang J, He XC, Tong WG, Johnson T, Wiedemann LM, Mishina Y, et al. Bone morphogenetic protein signaling inhibits hair follicle anagen induction by restricting epithelial stem/progenitor cell activation and expansion. Stem Cells. 2006;24(12):2826–39.PubMedCrossRefGoogle Scholar
  48. 48.
    Sieveking DP, Ng MK. Cell therapies for therapeutic angiogenesis: back to the bench. Vasc Med. 2009;14(2):153–66.PubMedCrossRefGoogle Scholar
  49. 49.
    Assis ACM, Carvalho JL, Jacoby BA, Ferreira RL, Castanheira P, Diniz SO, et al. Time-dependent migration of systemically delivered bone marrow mesenchymal stem cells to the infarcted heart. Cell Transplant. 2010;19(2):219–30.PubMedCrossRefGoogle Scholar
  50. 50.
    Kocher A, Schuster M, Bonaros N, Lietz K, Xiang G, Martens T, et al. Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/Gro CXC chemokines. J Mol Cell Cardiol. 2006;40(4):455–64.PubMedCrossRefGoogle Scholar
  51. 51.
    Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Deng J, Zou Z-M, Zhou T-L, Su Y-P, Ai G-P, Wang J-P, et al. Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue. Neurol Sci. 2011;32(4):641–51.PubMedCrossRefGoogle Scholar
  53. 53.
    Aghamir MK, Hosseini R, Alizadeh F. A vacuum device for penile elongation: fact or fiction?. BJU International. 2006 Apr;97(4):777–8.Google Scholar
  54. 54.
    Lévesque J-P, Hendy J, Takamatsu Y, Williams B, Winkler IG, Simmons PJ. Mobilization by either cyclophosphamide or granulocyte colony-stimulating factor transforms the bone marrow into a highly proteolytic environment. Exp Hematol. 2002;30(5):440–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol. 2002;3(7):687.PubMedCrossRefGoogle Scholar
  56. 56.
    Pusic I, DiPersio JF. Update on clinical experience with AMD3100, an SDF-1/CXCL12–CXCR4 inhibitor, in mobilization of hematopoietic stem and progenitor cells. Curr Opin Hematol. 2010;17(4):319–26.PubMedCrossRefGoogle Scholar
  57. 57.
    Chim H, Miller E, Gliniak C, Alsberg E. Stromal-cell-derived factor (SDF) 1-alpha in combination with BMP-2 and TGF-β1 induces site-directed cell homing and osteogenic and chondrogenic differentiation for tissue engineering without the requirement for cell seeding. Cell Tissue Res. 2012;350(1):89–94.PubMedCrossRefGoogle Scholar
  58. 58.
    Anthony BA, Link DC. Regulation of hematopoietic stem cells by bone marrow stromal cells. Trends Immunol. 2014;35(1):32–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505(7483):327–34.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D, et al. Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron. 1994;13(5):1071–82.PubMedCrossRefGoogle Scholar
  61. 61.
    Palmer TD, Takahashi J, Gage FH. The adult rat hippocampus contains primordial neural stem cells. Mol Cell Neurosci. 1997;8(6):389–404.PubMedCrossRefGoogle Scholar
  62. 62.
    Yin H, Price F, Rudnicki MA. Satellite cells and the muscle stem cell niche. Physiol Rev. 2013;93(1):23–67.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Lin G, Garcia M, Ning H, Banie L, Guo Y-L, Lue TF, et al. Defining stem and progenitor cells within adipose tissue. Stem Cells Dev. 2008;17(6):1053–63.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Bussolati B, Bruno S, Grange C, Buttiglieri S, Deregibus MC, Cantino D, et al. Isolation of renal progenitor cells from adult human kidney. Am J Pathol. 2005;166(2):545–55.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Wu C, Xie Y, Gao F, Wang Y, Guo Y, Tian H, et al. Lgr5 expression as stem cell marker in human gastric gland and its relatedness with other putative cancer stem cell markers. Gene. 2013;525(1):18–25.PubMedCrossRefGoogle Scholar
  66. 66.
    Barker N, Van Es JH, Kuipers J, Kujala P, Van Den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449(7165):1003.PubMedCrossRefGoogle Scholar
  67. 67.
    da Silva-Diz V, Sole-Sanchez S, Valdes-Gutierrez A, Urpi M, Riba-Artes D, Penin R, et al. Progeny of Lgr5-expressing hair follicle stem cell contributes to papillomavirus-induced tumor development in epidermis. Oncogene. 2013;32(32):3732.PubMedCrossRefGoogle Scholar
  68. 68.
    Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, et al. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science. 2010;327(5971):1385–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Lin C-S, Xin Z-C, Deng C-H, Ning H, Lin G, Lue TF. Defining adipose tissue-derived stem cells in tissue and in culture. Histol Histopathol. 2010;25(6):2010.Google Scholar
  70. 70.
    Loera-Valencia R, Wang X-Y, Wright GW, Barajas-López C, Huizinga JD. Ano1 is a better marker than c-Kit for transcript analysis of single interstitial cells of Cajal in culture. Cell Mol Biol Lett. 2014;19(4):601.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Zhang H, Lin G, Qiu X, Ning H, Banie L, Lue TF, et al. Label retaining and stem cell marker expression in the developing rat urinary bladder. Urology. 2012;79(3):746.e1–6.PubMedGoogle Scholar
  72. 72.
    Lv F-J, Tuan RS, Cheung KM, Leung VY. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells. 2014;32(6):1408–19.PubMedCrossRefGoogle Scholar
  73. 73.
    Kurzrock EA, Lieu DK, DeGraffenried LA, Chan CW, Isseroff RR. Label-retaining cells of the bladder: candidate urothelial stem cells. Am J Physiol Renal Physiol. 2008;294(6):F1415–21.PubMedCrossRefGoogle Scholar
  74. 74.
    Huang YL, Tao X, Xia J, Li CY, Cheng B. Distribution and quantity of label-retaining cells in rat oral epithelia. J Oral Pathol Med. 2009;38(8):663–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Cotsarelis G, Sun T-T, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990;61(7):1329–37.PubMedCrossRefGoogle Scholar
  76. 76.
    Salic A, Mitchison TJ. A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc Natl Acad Sci. 2008;105(7):2415–20.PubMedCrossRefGoogle Scholar
  77. 77.
    Toma JG, Akhavan M, Fernandes KJ, Barnabé-Heider F, Sadikot A, Kaplan DR, et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol. 2001;3(9):778.PubMedCrossRefGoogle Scholar
  78. 78.
    Toma JG, McKenzie IA, Bagli D, Miller FD. Isolation and characterization of multipotent skin-derived precursors from human skin. Stem Cells. 2005;23(6):727–37.PubMedCrossRefGoogle Scholar
  79. 79.
    Bartsch G Jr, Yoo JJ, De Coppi P, Siddiqui MM, Schuch G, Pohl HG, et al. Propagation, expansion, and multilineage differentiation of human somatic stem cells from dermal progenitors. Stem Cells Dev. 2005;14(3):337–48.PubMedCrossRefGoogle Scholar
  80. 80.
    Mittermayr R, Antonic V, Hartinger J, Kaufmann H, Redl H, Téot L, et al. Extracorporeal shock wave therapy (ESWT) for wound healing: technology, mechanisms, and clinical efficacy. Wound Repair Regen. 2012;20(4):456–65.PubMedGoogle Scholar
  81. 81.
    Lai J-P, Wang F-S, Hung C-M, Wang C-J, Huang C-J, Kuo Y-R. Extracorporeal shock wave accelerates consolidation in distraction osteogenesis of the rat mandible. J Trauma Acute Care Surg. 2010;69(5):1252–8.CrossRefGoogle Scholar
  82. 82.
    Moretti B, Notarnicola A, Moretti L, Giordano P, Patella V. A volleyball player with bilateral knee osteochondritis dissecans treated with extracorporeal shock wave therapy. Musculoskelet Surg. 2009;93(1):37–41.CrossRefGoogle Scholar
  83. 83.
    Aicher A, Heeschen C, Sasaki K-i, Urbich C, Zeiher AM, Dimmeler S. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia. Circulation. 2006;114(25):2823–30.PubMedCrossRefGoogle Scholar
  84. 84.
    Wilner JM, Strash WW. Extracorporeal shockwave therapy for plantar fasciitis and other musculoskeletal conditions utilizing the Ossatron—an update. Clin Podiatr Med Surg. 2004;21(3):441–7, viii.PubMedCrossRefGoogle Scholar
  85. 85.
    Vardi Y, Appel B, Kilchevsky A, Gruenwald I. Does low intensity extracorporeal shock wave therapy have a physiological effect on erectile function? short-term results of a randomized, double-blind, sham controlled study. J Urol. 2012;187(5):1769–75.PubMedCrossRefGoogle Scholar
  86. 86.
    Liu J, Zhou F, Li G-Y, Wang L, Li H-X, Bai G-Y, et al. Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats. Int J Mol Sci. 2013;14(5):10661–73.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Chen YJ, Wurtz T, Wang CJ, Kuo YR, Yang KD, Huang HC, et al. Recruitment of mesenchymal stem cells and expression of TGF-β1 and VEGF in the early stage of shock wave-promoted bone regeneration of segmental defect in rats. J Orthop Res. 2004;22(3):526–34.PubMedCrossRefGoogle Scholar
  88. 88.
    Qiu X, Lin G, Xin Z, Ferretti L, Zhang H, Lue TF, et al. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med. 2013;10(3):738–46.PubMedCrossRefGoogle Scholar
  89. 89.
    Jones NC, Tyner KJ, Nibarger L, Stanley HM, Cornelison DD, Fedorov YV, et al. The p38α/β MAPK functions as a molecular switch to activate the quiescent satellite cell. J Cell Biol. 2005;169(1):105–16.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Oh J-E, Bae G-U, Yang Y-J, Yi M-J, Lee H-J, Kim B-G, et al. Cdo promotes neuronal differentiation via activation of the p38 mitogen-activated protein kinase pathway. FASEB J. 2009;23(7):2088–99.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Xu Y, Guan R, Lei H, Gao Z, Li H, Hui Y, et al. Implications for differentiation of endogenous stem cells: therapeutic effect from icariside II on a rat model of postprostatectomy erectile dysfunction. Stem Cells Dev. 2014;24(6):747–55.PubMedCrossRefGoogle Scholar
  92. 92.
    Zhang J, Li A-M, Liu B-X, Han F, Liu F, Sun S-P, et al. Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO–cGMP pathway. Asian J Androl. 2013;15(1):143.PubMedCrossRefGoogle Scholar
  93. 93.
    Song J, Shu L, Zhang Z, Tan X, Sun E, Jin X, et al. Reactive oxygen species-mediated mitochondrial pathway is involved in Baohuoside I-induced apoptosis in human non-small cell lung cancer. Chemico-Biol Interact. 2012;199(1):9–17.CrossRefGoogle Scholar
  94. 94.
    Zampetaki A, Kirton JP, Xu Q. Vascular repair by endothelial progenitor cells. Cardiovasc Res. 2008;78(3):413–21.PubMedCrossRefGoogle Scholar
  95. 95.
    Foresta C, Caretta N, Lana A, Cabrelle A, Palu G, Ferlin A. Circulating endothelial progenitor cells in subjects with erectile dysfunction. Int J Impot Res. 2005;17(3):288.PubMedCrossRefGoogle Scholar
  96. 96.
    Aghamir SM, Hosseini SR, Gooran S. Totally tubeless percutaneous nephrolithotomy. J Endourol. 2004 Sep 1;18(7):647–8.Google Scholar
  97. 97.
    Gur S, Kadowitz PJ, Hellstrom WJ. A critical appraisal of erectile function in animal models of diabetes mellitus. Int J Androl. 2009;32(2):93–114.PubMedCrossRefGoogle Scholar
  98. 98.
    Winiarska K, Fraczyk T, Malinska D, Drozak J, Bryla J. Melatonin attenuates diabetes-induced oxidative stress in rabbits. J Pineal Res. 2006;40(2):168–76.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Urology Research CenterTehran University of Medical SciencesTehranIran

Personalised recommendations