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Novel mechanism of gene transfection by low-energy shock wave.

ABSTRACT: Extracorporeal shock wave (SW) therapy has been studied in the transfection of naked nucleic acids into various cell lines through the process of sonoporation, a process that affects the permeation of cell membranes, which can be an effect of cavitation. In this study, siRNAs were efficiently transfected into primary cultured cells and mouse tumor tissue via SW treatment. Furthermore SW-induced siRNA transfection was not mediated by SW-induced sonoporation, but by microparticles (MPs) secreted from the cells. Interestingly, the transfection effect of the siRNAs was transferable through the secreted MPs from human umbilical vein endothelial cell (HUVEC) culture medium after treatment with SW, into HUVECs in another culture plate without SW treatment. In this study, we suggest for the first time a mechanism of gene transfection induced by low-energy SW through secreted MPs, and show that it is an efficient physical gene transfection method in vitro and represents a safe therapeutic strategy for site-specific gene delivery in vivo.

SUBMITTER: Ha CH

PROVIDER: S-EPMC4525295 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Novel mechanism of gene transfection by low-energy shock wave.

Ha Chang Hoon CH Lee Seok Cheol SC Kim Sunghyen S Chung Jihwa J Bae Hasuk H Kwon Kihwan K

Scientific reports 20150805

Extracorporeal shock wave (SW) therapy has been studied in the transfection of naked nucleic acids into various cell lines through the process of sonoporation, a process that affects the permeation of cell membranes, which can be an effect of cavitation. In this study, siRNAs were efficiently transfected into primary cultured cells and mouse tumor tissue via SW treatment. Furthermore SW-induced siRNA transfection was not mediated by SW-induced sonoporation, but by microparticles (MPs) secreted f ...[more]

PMID: 26243452

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Project description:BACKGROUND: There are several treatment options for calcifying tendinitis of the shoulder. The next step treatment after conservative treatment fails is still a matter of dispute. Extracorporeal shock wave therapy (ESWT) has been shown to be a good alternative to surgery, but the best treatment intensity remains unknown. High-energy ESWT is much more painful, more expensive, and usually is done in an inpatient setting, whereas low-energy ESWT can be performed in an outpatient setting by a physical therapist. QUESTIONS/PURPOSES: A systematic review and meta-analysis of randomized trials was performed to answer two clear research questions: (1) Is there a greater increase in the Constant-Murley score in patients treated with high-energy ESWT compared with those treated with low-energy ESWT by 3 months and by 6 months? (2) Is there a greater chance of complete resorption of the calcifications in patients treated with high-energy ESWT compared with those treated with low-energy ESWT by 3 months and by 6 months? METHODS: Five relevant electronic online databases, Medline (through PubMed), EMBASE (through OVID), Cinahl (through EBSCO), Web of Science, and the Cochrane Central Register of Controlled Trials, were systematically searched. We also crosschecked the reference lists of articles and reviews for possible relevant studies. Eligible for inclusion were all randomized controlled trials (RCTs) that compared high-energy ESWT (> 0.28 mJ/mm(2)) with low-energy ESWT (< 0.08 mJ/mm(2)). One author examined titles and abstracts of each identified study to assess study eligibility. Two reviewers independently extracted data and assessed the risk of bias and study quality. The primary outcome measure, the Constant-Murley score, was assessed by comparing mean functional outcome scores between the groups. Secondary outcomes were assessed using odds ratios, when appropriate data were pooled. Based on this process, five RCTs (359 participants) were included. RESULTS: All five RCTs showed greater improvement in functional outcome (Constant-Murley score) in patients treated with high-energy ESWT compared with patients treated with low-energy ESWT at 3 and 6 months. The 3-month mean difference was 9.88 (95% CI, 9.04-10.72, p < 0.001; 6-month data could not be pooled). Furthermore, high-energy ESWT more often resulted in complete resorption of the deposits at 3 months. The corresponding odds ratio was 3.40 (95% CI, 1.35-8.58) and p = 0.009 (6-month data could not be pooled). CONCLUSION: When shock wave therapy is chosen, high-energy shock wave therapy is more likely to result in improved Constant-Murley score and resorption of the deposits compared with low-energy therapy. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Project description:Conflicting reports in the literature have raised the question whether radial extracorporeal shock wave therapy (rESWT) devices and vibrating massage devices have similar energy signatures and, hence, cause similar bioeffects in treated tissues.We used laser fiber optic probe hydrophone (FOPH) measurements, high-speed imaging and x-ray film analysis to compare fundamental elements of the energy signatures of two rESWT devices (Swiss DolorClast; Electro Medical Systems, Nyon, Switzerland; D-Actor 200; Storz Medical, Tägerwillen, Switzerland) and a vibrating massage device (Vibracare; G5/General Physiotherapy, Inc., Earth City, MO, USA). To assert potential bioeffects of these treatment modalities we investigated the influence of rESWT and vibrating massage devices on locomotion ability of Caenorhabditis elegans (C. elegans) worms.FOPH measurements demonstrated that both rESWT devices generated acoustic waves with comparable pressure and energy flux density. Furthermore, both rESWT devices generated cavitation as evidenced by high-speed imaging and caused mechanical damage on the surface of x-ray film. The vibrating massage device did not show any of these characteristics. Moreover, locomotion ability of C. elegans was statistically significantly impaired after exposure to radial extracorporeal shock waves but was unaffected after exposure of worms to the vibrating massage device.The results of the present study indicate that both energy signature and bioeffects of rESWT devices are fundamentally different from those of vibrating massage devices.Prior ESWT studies have shown that tissues treated with sufficient quantities of acoustic sound waves undergo cavitation build-up, mechanotransduction, and ultimately, a biological alteration that "kick-starts" the healing response. Due to their different treatment indications and contra-indications rESWT devices cannot be equated to vibrating massage devices and should be used with due caution in clinical practice.

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Novel mechanism of gene transfection by low-energy shock wave.

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Novel mechanism of gene transfection by low-energy shock wave.

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