Lin G et al, 2017: In Situ Activation of Penile Progenitor Cells With Low-Intensity Extracorporeal Shockwave Therapy.
Lin G, Reed-Maldonado AB, Wang B, Lee YC, Zhou J, Lu Z, Wang G, Banie L, Lue TF.
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA.
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/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 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. Lin G, Reed-Maldonado HB, Wang B, et al. In Situ Activation of Penile Progenitor Cells With Low-Intensity Extracorporeal Shockwave Therapy. J Sex Med 2017;XX:XXX-XXX.
J Sex Med. 2017 Feb 28. pii: S1743-6095(17)30083-8. doi: 10.1016/j.jsxm.2017.02.004. [Epub ahead of print]
Since several years the Lab in San Francisco is working experimentally on that subject. Their studies have not offered a breakthrough view on Li-ESWT but they have continuously added knowledge about the possible mechanisms involved in amelioration of ED seen in some clinical studies. The present study adds to the principle of treating the underlying pathophysiology.
During the recent 2017 AUA congress in Boston the senior author Tom Lue participated in a Point-Counterpoint debate: “Erectile Dysfunction and the Shocking Truth: Is Shockwave Therapy Effective?”
The Webcast can be entered free of charge on the AUA home page (http://www.aua2017.org/). The debate adds in an entertaining way to the understanding of the subject and I recommend a visit. (http://www.aua2017.org/webcasts/webcast_play.cfm?videoID=5435&agendaid=14036&id=13995,13998,14197,14198,14199,14203,14204,14205,14036,14104,14843)