title: In Situ Activation of Penile Progenitor Cells With Low-Intensity Extracorporeal Shockwave Therapy.
abstract: We previously reported that progenitor cells, or stem cells, exist within penile tissue. We hypothesized that acoustic wave stimulation by low-intensity extracorporeal shockwave therapy (Li-ESWT) would activate local stem or progenitor cells within the penis, producing regenerative effects.
  
  
  
  To study the feasibility of in situ penile progenitor cell activation by Li-ESWT.
  
  
  
  We performed a cohort analysis of young and middle-age male Sprague-Dawley rats treated with 5-ethynyl-2'-deoxyuridine (EdU) pulse followed by Li-ESWT. In addition, Li-ESWT was applied to cultured Schwann cells and endothelial cells to study the molecular mechanism involved in cell proliferation. Thirty minutes before Li-ESWT, each rat received an intraperitoneal injection of EdU. Li-ESWT was applied to the penis at very low (0.02 mJ/mm2at 3 Hz for 300 pulses) or low (0.057 mJ/mm2at 3 Hz for 500 pulses) energy levels. The endothelial and Schwann cells were treated with very low energy (0.02 mJ/mm2at 3 Hz for 300 pulses) in vitro.
  
  
  
  At 48 hours or 1 week after Li-ESWT, penile tissues were harvested for histologic study to assess EdU+and Ki-67+cells, and cell proliferation, Ki-67 expression, Erk1/2 phosphorylation, translocation, and angiogenesis were examined in cultured Schwann and endothelial cells after Li-ESWT.
  
  
  
  Li-ESWT significantly increased EdU+cells within penile erectile tissues (P < .01) at 48 hours and 1 week. There were more cells activated in young animals than in middle-age animals, and the effect depended on dosage. Most activated cells were localized within subtunical spaces. In vitro studies indicated that Li-ESWT stimulated cell proliferation through increased phosphorylation of Erk1/2.
  
  
  
  The present results provide a possible explanation for the clinical benefits seen with Li-ESWT.
  
  
  
  The main limitation of the present project was the short period of study and the animal model used. Li-ESWT could be less effective in improving erectile function in old animals because of the decreased number and quality of penile stem or progenitor cells associated with aging.
  
  
  
  Li-ESWT activation of local penile progenitor cells might be one of the mechanisms that contribute to the beneficial effects of shockwave treatment for erectile dysfunction, which represents a non-invasive alternative to exogenous stem cell therapy. Lin G, Reed-Maldonado AB, Wang B, et al. In Situ Activation of Penile Progenitor Cells With Low-Intensity Extracorporeal Shockwave Therapy. J Sex Med 2017;14:493-501.
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Reed-Maldonado
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA; Department of Urology, The Second Hospital, Zhejiang University, Zhejiang, China.
authors.forename: Bohan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA; Department of Urology, Kaohsiung Medical University Hospital, and Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yung-Chin
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA; Department of Urology, The Third XiangYa Hospital, Central South University, Changsha, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA; Department of Urology, The First Hospital of Jilin University, Changchun, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Guifang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Lia
authors.initials: L
authors.lastname: Banie
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA. Electronic address: Tom.Lue@ucsf.edu.
authors.forename: Tom F
authors.initials: TF
authors.lastname: Lue
mesh_terms: D000818:Animals; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D007172:Erectile Dysfunction / Q000378:metabolism / Q000628:therapy*; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism; D013234:Stem Cells
chemical_list: C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: Endogenous Stem Cells; Erectile Dysfunction; Low-Intensity Extracorporeal Shockwave Therapy; Penile Progenitor Cells; Stem Cells