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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.

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α), and enhanced activating transcription factor 4 (ATF4) in an energy-dependent manner. In addition, GSK2656157—an inhibitor of PERK—effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF)1α or glial cell-derived neurotrophic factor (GDNF) in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy.

In this clinical study, data analyses suggest that this new absorbable hyaluronan hydrogel, as nasal dressing/packing after ESS is safe and promotes the postoperative reepithelization process and reduces the presence of synechia, edema, crust, and mild mucopurulent drainage.

In conclusion, this experiment reveals that rat uMDSCs can be isolated successfully and can form myotubes in vitro. PERK/ATF4 pathway was involved in myotube formation, and L6 rat myoblast cells were activated by Li-ESWT to form myotubes. These findings suggest that PERK/ATF4 pathway is activated by Li-ESWT. This study elucidates one of the biochemical pathways responsible for the clinical improvements seen after Li-ESWT. It is possible that this information will help to establish Li-ESWT as an acceptable treatment modality and may help to further refine the use of Li-ESWT in the clinical practice of medicine.

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Objectives To evaluate the therapeutic effect of once-per-week low-intensity extracorporeal shock wave therapy (Li-ESWT) on underactive bladder (UAB) in the streptozotocin-induced diabetic rat model. Materials and Methods Thirty-six female Sprague-Dawley rats were assigned into 3 groups: normal control (NC), diabetes control (DMC), and diabetes underwent Li-ESWT (DM Li-ESWT). The two DM groups received intraperitoneal 60 mg/kg streptozotocin injection to induce diabetes mellitus. The Li-ESWT was applied toward the pelvis of the rats started 4 weeks after the streptozotocin administration and lasted for 4 weeks. The shock wave therapy was given once-per-week with energy flux density of 0.02 mJ/mm2 at 3 Hz for 400 pulses. All rats were subjected to conscious cystometry, leak point pressure, ex-vivo organ bath study, histology, immunofluorescence, and western blot analysis. Results Conscious cystometry revealed voiding dysfunction in DMC group, whereas DM Li-ESWT group showed significantly improved voiding function in reduced post-void residual urine and increased leak point pressure compared to DMC group. Ex-vivo organ bath study showed that Li-ESWT enhances muscle contractile activity (MCA) of bladder and urethra in electrical field stimulation (EFS) and drug stimulation. Histologically, Li-ESWT significantly restored bladder morphology in reducing intravesical lumen area and increasing muscle proportion of the bladder wall. Western blot analysis showed higher smooth muscle actin (SMA) expression of bladder wall in DM Li-ESWT compared to DMC group. Immunofluorescence showed decreased nerve-ending distribution, and destroyed and shortened nerve fibers in DMC group and recovery of neuronal integrity and innervation in DM Li-ESWT group. Conclusions In conclusion, Li-ESWT ameliorated underactive bladder and urinary incontinence in the diabetic UAB rat model. The improvement seems to be the results of restoration of bladder and urethra structure and function by Li-ESWT. Li-ESWT is non-invasive and may become a better alternative therapy for UAB. Further investigations are warranted.

ZF rats can serve as an animal model in which to study OAED. This study reveals that obesity impairs erectile function by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation in the corpus cavernosum. Li-ESWT restored penile haemodynamic parameters in the ZF rats by restoring smooth muscle and endothelium content and reducing lipid accumulation. The underlying mechanism of Li-ESWT appears to be activation of stem/progenitor cells, which prompts cellular proliferation and accelerates penile tissue regeneration. Our findings are of interest, not just as a validation of this emerging treatment for erectile dysfunction, but also as a novel and potentially significant method to modulate endogenous stem/progenitor cells in other disease processes.