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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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>To study the feasibility of in situ penile progenitor cell activation by Li-ESWT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a cohort analysis of young and middle-age male Sprague-Dawley rats treated with 5-ethynyl-2\u2032-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\/mm2 at 3 Hz for 300 pulses) or low (0.057 mJ\/mm2 at 3 Hz for 500 pulses) energy levels. The endothelial and Schwann cells were treated with very low energy (0.02 mJ\/mm2 at 3 Hz for 300 pulses) in\u00a0vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcomes<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Li-ESWT significantly increased EdU+ cells within penile erectile tissues (P &amp;lt; .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\u00a0vitro studies indicated that Li-ESWT stimulated cell proliferation through increased phosphorylation of Erk1\/2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Translation<\/jats:title>\n                  <jats:p>The present results provide a possible explanation for the clinical benefits seen with Li-ESWT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Strengths and Limitations<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1016\/j.jsxm.2017.02.004","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T19:15:55Z","timestamp":1488395755000},"page":"493-501","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":59,"title":["In Situ Activation of Penile Progenitor Cells with Low-Intensity Extracorporeal 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