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The Paracrine Function of Mesenchymal Stem Cells in Response to Pulsed Focused Ultrasound
Mehdi Razavi1,2,3, Melika Rezaee1, Arsenii Telichko1
1Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, 6429Stanford University, Palo Alto, CA, USA.
Abstract:
We studied the paracrine function of mesenchymal stem cells (MSCs) derived from various sources in response to pulsed focused ultrasound (pFUS). Human adipose tissue (AD), bone marrow (BM), and umbilical cord (UC) derived MSCs were exposed to pFUS at two intensities: 0.45 W/cm2 ISATA (310 kPa PNP) and 1.3 W/cm2 ISATA (540 kPa PNP). Following pFUS, the viability and proliferation of MSCs were assessed using a hemocytometer and confocal microscopy, and their secreted cytokine profile determined using a multiplex ELISA. Our findings showed that pFUS can stimulate the production of immunomodulatory, anti-inflammatory, and angiogenic cytokines from MSCs which was dependent on both the source of MSC being studied and the acoustic intensity employed. These important findings set the foundation for additional mechanistic and validation studies using this novel noninvasive and clinically translatable technology for modulating MSC biology.
Insights
Pulsed focused ultrasound (pFUS) noninvasively modulates mesenchymal stem cells (MSCs). This technology stimulates the release of therapeutic cytokines from MSCs, with effects varying by MSC source and ultrasound intensity.
Area of Science:
- Regenerative Medicine
- Biotechnology
- Biophysics
Background:
- Mesenchymal stem cells (MSCs) possess paracrine functions with therapeutic potential.
- Modulating MSC paracrine function noninvasively is a key challenge in regenerative medicine.
- Pulsed focused ultrasound (pFUS) is an emerging technology for biological applications.
Purpose of the Study:
- To investigate the effect of pFUS on the paracrine function of MSCs from different sources.
- To determine the influence of pFUS intensity on MSC response.
- To assess the potential of pFUS as a tool for modulating MSC-based therapies.
Main Methods:
- MSCs were isolated from human adipose tissue (AD), bone marrow (BM), and umbilical cord (UC).
- MSCs were exposed to pFUS at two acoustic intensities (0.45 W/cm² and 1.3 W/cm²).
- MSC viability, proliferation, and secreted cytokine profiles were analyzed.
Main Results:
- pFUS stimulation resulted in increased production of immunomodulatory, anti-inflammatory, and angiogenic cytokines.
- The MSC response to pFUS was dependent on the source of MSCs (AD, BM, UC).
- Acoustic intensity of pFUS significantly influenced the cytokine secretion profile.
Conclusions:
- pFUS is a viable noninvasive technology for modulating MSC paracrine function.
- The study highlights the potential for tailoring pFUS parameters for specific therapeutic outcomes.
- These findings provide a foundation for further research into pFUS-mediated MSC modulation for clinical applications.
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