Background: 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.
Aims: To study the feasibility of in situ penile progenitor cell activation by Li-ESWT.
Methods: 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/mm(2) at 3 Hz for 300 pulses) or low (0.057 mJ/mm(2) at 3 Hz for 500 pulses) energy levels. The endothelial and Schwann cells were treated with very low energy (0.02 mJ/mm(2) at 3 Hz for 300 pulses) in vitro.
Outcomes: 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.
Results: 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.
Clinical Translation: The present results provide a possible explanation for the clinical benefits seen with Li-ESWT.
Strengths and Limitations: 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.
Conclusion: 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.
[1]Univ Calif San Francisco, Sch Med, Dept Urol, Knuppe Mol Urol Lab, San Francisco, CA 94143 USA.
[2]Zhejiang Univ, Hosp 2, Dept Urol, Hangzhou, Zhejiang, Peoples R China.
[3]Kaohsiung Med Univ Hosp, Dept Urol, Kaohsiung, Taiwan.
[4]Kaohsiung Med Univ, Coll Med, Fac Med, Dept Urol, Kaohsiung, Taiwan.
[5]Cent S Univ, XiangYa Hosp 3, Dept Urol, Changsha, Hunan, Peoples R China.
[6]Jilin Univ, Hosp 1, Dept Urol, Changchun, Peoples R China.
(8.0+极速模式)