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  3. Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles

Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles

  • Cell Mol Biol Lett. 2023 Jan 30;28(1):9. doi: 10.1186/s11658-023-00422-3.
Xueke Li # 1 2 3,  Yi Zhong # 1 2 3,  Wuqi Zhou 1 2 3,  Yishu Song 1 2 3,  Wenqu Li 1 2 3,  Qiaofeng Jin 1 2 3,  Tang Gao 1 2 3,  Li Zhang 4 5 6,  Mingxing Xie 7 8 9
Affiliations

Affiliations

  • 1 Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Clinical Research Center for Medical Imaging in Hubei Province, Wuhan, 430022, China.
  • 3 Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
  • 4 Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. zli429@hust.edu.cn.
  • 5 Clinical Research Center for Medical Imaging in Hubei Province, Wuhan, 430022, China. zli429@hust.edu.cn.
  • 6 Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China. zli429@hust.edu.cn.
  • 7 Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xiemx@hust.edu.cn.
  • 8 Clinical Research Center for Medical Imaging in Hubei Province, Wuhan, 430022, China. xiemx@hust.edu.cn.
  • 9 Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China. xiemx@hust.edu.cn.
  • # Contributed equally.
PMID: 36717768 DOI: 10.1186/s11658-023-00422-3
Abstract

Background: Bone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is finite and they usually bear specific repertoires of bioactive molecules to perform manifold cell-cell communication, but not one particular therapeutic function as expected, their practical application is still limited. Strategies are needed to increase the production of EVs and enhance their therapeutic function. Recent studies have suggested that low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive method to increase the secretion of EVs and promote their anti-inflammatory effects. However, the effect of LIPUS stimulation of BMSCs on EVs derived from the cells remains unclear. The objective of this study was to investigate whether LIPUS stimulation on BMSCs could increase the secretion of EVs and enhance their anti-inflammatory effects.

Methods: BMSCs were exposed to LIPUS (300 mW/cm2) for 15 min and EVs were isolated by ultracentrifugation. Anti-inflammatory effects of EVs were investigated on RAW264.7 cells in vitro and in the allogeneic skin transplantation model. Small RNA-seq was utilized to identify components difference in EVs with/without LIPUS irradiation.

Results: In this study, we found that LIPUS stimulation could lead to a 3.66-fold increase in the EVs release from BMSCs. Moreover, both in vitro and in vivo experimental results suggested that EVs secreted from LIPUS-treated BMSCs (LIPUS-EVs) possessed stronger anti-inflammatory function than EVs secreted from BMSCs without LIPUS stimulation (C-EVs). RNA-seq analysis revealed that miR-328-5p and miR-487b-3p were significantly up-regulated in LIPUS-EVs compare with C-EVs. The suppression of MAPK signaling pathway by these two up-regulated miRNAs could be the potential mechanism of strengthened anti-inflammatory effects of LIPUS-EVs.

Conclusion: LIPUS stimulation on BMSCs could significantly increase the secretion of EVs. Moreover, EVs generated from LIPUS-treated BMSCs possessed much stronger anti-inflammatory function than C-EVs. Therefore, LIPUS could be a promising non-invasive strategy to promote the production of EVs from BMSCs and augment their anti-inflammatory effects.

Keywords

Bone marrow mesenchymal stem cells; Extracellular vesicles; Inflammation; Low-intensity pulsed ultrasound; microRNA.

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