scholarly journals Low-Intensity Pulsed Ultrasound-Generated Singlet Oxygen Induces Telomere Damage Leading to Glioma Stem Cell Awakening From Quiescence

Author(s):  
Sirong Song ◽  
Dongbin Ma ◽  
Lixia Xu ◽  
Qiong Wang ◽  
Lanxiang Liu ◽  
...  

Abstract Background: Cancer stem cells, quiescent and drug-resistant, have become a therapeutic target. Low-intensity pulsed ultrasound (LIPUS), a new noninvasive physical device, promotes pluripotent stem cell differentiation and is mainly applied in tissue engineering but rarely in oncotherapy. We explored the effect and mechanism of LIPUS on glioma stem cell (GSC) expulsion from quiescence.Methods: Immunofluorescence staining and flow cytometry were used to detect changes of stem hallmarkers. RT-PCR results showed the gene expression levels of stem-related transcription factors. Brud and RNA-seq were performed for cell cycle analysis. Western blotting showed different expressions of key point proteins. Telomeres damage was found by FISH and IF-FISH. Fluorescence detection was used for mitochondrial membrane potential assay and singlet oxygen detection. Tumor xenograft and immunohistochemical staining were performed to confirm the role of low intensity pulsed ultrasound.Results: We found that LIPUS led to attenuated expression of GSC hallmarks, promoted GSC escape from G0 quiescence, and significantly weakened the stemness-related Wnt and Hh pathways. Next, Interestingly, LIPUS transferred sonomechanical energy into recombinant cytochrome C and B5 proteins in vitro, which converted oxygen molecules into singlet oxygen, triggering a telomere crisis. The results in vivo and in vitro confirmed that LIPUS enhanced GSC sensitivity to temozolomide.Conclusion: These results demonstrated that LIPUS “wakes up” GSCs to improve chemotherapy by transferring energy to cyt families and leading to telomere crisis.

2021 ◽  
Vol 30 ◽  
pp. 096368972098614
Author(s):  
Peng Xia ◽  
Xinwei Wang ◽  
Qi Wang ◽  
Xiaoju Wang ◽  
Qiang Lin ◽  
...  

Mesenchymal stem cell (MSC) migration is promoted by low-intensity pulsed ultrasound (LIPUS), but its mechanism is unclear. Since autophagy is known to regulate cell migration, our study aimed to investigate if LIPUS promotes the migration of MSCs via autophagy regulation. We also aimed to investigate the effects of intra-articular injection of MSCs following LIPUS stimulation on osteoarthritis (OA) cartilage. For the in vitro study, rat bone marrow-derived MSCs were treated with an autophagy inhibitor or agonist, and then they were stimulated by LIPUS. Migration of MSCs was detected by transwell migration assays, and stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR4) protein levels were quantified. For the in vivo study, a rat knee OA model was generated and treated with LIPUS after an intra-articular injection of MSCs with autophagy inhibitor added. The cartilage repair was assessed by histopathological analysis and extracellular matrix protein expression. The in vitro results suggest that LIPUS increased the expression of SDF-1 and CXCR4, and it promoted MSC migration. These effects were inhibited and enhanced by autophagy inhibitor and agonist, respectively. The in vivo results demonstrate that LIPUS significantly enhanced the cartilage repair effects of MSCs on OA, but these effects were blocked by autophagy inhibitor. Our results suggest that the migration of MSCs was enhanced by LIPUS through the activation autophagy, and LIPUS improved the protective effect of MSCs on OA cartilage via autophagy regulation.


2009 ◽  
Vol 17 ◽  
pp. S102-S103
Author(s):  
K. Uenaka ◽  
S. Imai ◽  
S. Shioji ◽  
K. Kumagai ◽  
N. Okumura ◽  
...  

Micromachines ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1488
Author(s):  
Colleen McCarthy ◽  
Gulden Camci-Unal

As explained by Wolff’s law and the mechanostat hypothesis, mechanical stimulation can be used to promote bone formation. Low intensity pulsed ultrasound (LIPUS) is a source of mechanical stimulation that can activate the integrin/phosphatidylinositol 3-OH kinase/Akt pathway and upregulate osteogenic proteins through the production of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). This paper analyzes the results of in vitro and in vivo studies that have evaluated the effects of LIPUS on cell behavior within three-dimensional (3D) titanium, ceramic, and hydrogel scaffolds. We focus specifically on cell morphology and attachment, cell proliferation and viability, osteogenic differentiation, mineralization, bone volume, and osseointegration. As shown by upregulated levels of alkaline phosphatase and osteocalcin, increased mineral deposition, improved cell ingrowth, greater scaffold pore occupancy by bone tissue, and superior vascularization, LIPUS generally has a positive effect and promotes bone formation within engineered scaffolds. Additionally, LIPUS can have synergistic effects by producing the piezoelectric effect and enhancing the benefits of 3D hydrogel encapsulation, growth factor delivery, and scaffold modification. Additional research should be conducted to optimize the ultrasound parameters and evaluate the effects of LIPUS with other types of scaffold materials and cell types.


2020 ◽  
Vol 15 (5) ◽  
pp. 462-472 ◽  
Author(s):  
Abdollah Amini ◽  
Sufan Chien ◽  
Mohammad Bayat

Objective: This is a systematic review of the effects of low-intensity pulsed ultrasound (LIPUS) on stem cell differentiation. Background Data: Recent studies have investigated several types of stem cells from different sources in the body. These stem cells should strictly be certified and promoted for cell therapies before being used in medical applications. LIPUS has been used extensively in treatment centers and in research to promote stem cell differentiation, function, and proliferation. Materials and Methods: The databases of PubMed, Google Scholar, and Scopus were searched for abstracts and full-text scientific papers published from 1989-2019 that reported the application of LIPUS on stem cell differentiation. Related English language articles were found using the following defined keywords: low-intensity pulsed ultrasound, stem cell, differentiation. Criteria for inclusion in the review were: LIPUS with frequencies of 1–3 MHz and pulsed ultrasound intensity of <500 mW/cm2. Duration, exposure time, and cell sources were taken into consideration. Results: Fifty-two articles were selected based on the inclusion criteria. Most articles demonstrated that the application of LIPUS had positive effects on stem cell differentiation. However, some authors recommended that LIPUS combined with other physical therapy aides was more effective in stem cell differentiation. Conclusions: LIPUS significantly increases the level of stem cell differentiation in cells derived mainly from bone marrow mesenchymal stem cells. There is a need for further studies to analyze the effect of LIPUS on cells derived from other sources, particularly adipose tissue-derived mesenchymal stem cells, for treating hard diseases, such as osteoporosis and diabetic foot ulcer. Due to a lack of reporting on standard LIPUS parameters in the field, more experiments comparing the protocols for standardization of LIPUS parameters are needed to establish the best protocol, which would allow for the best results.


2010 ◽  
Vol 36 (5) ◽  
pp. 743-751 ◽  
Author(s):  
Yi-Sheng Chan ◽  
Kuo-Yao Hsu ◽  
Chia-Hua Kuo ◽  
Shin-Da Lee ◽  
Su-Ching Chen ◽  
...  

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