High-frequency sounds can change basic stem cells into functional bone matter
Researchers from Royal Melbourne Institute of Technology (RMIT) University, Australia, have utilized high-frequency sound waves in a novel treatment to turn stem cells into bone cells in hopes of helping patients with cancer or degenerative diseases regrow their bones via tissue engineering.
Tissue engineering is an emerging field in biology which focuses on the regeneration, restoration, or improvement of biological tissues.
Research into restoring bone tissue requires large quantities of stem cells. While some studies have utilized bone marrow stem cells in the course of their research, these cells are excruciatingly painful to extract.
The team of researchers in Australia focused on using sound waves to trigger stem cells to differentiate into different cell fates. The method utilizes the human body’s natural ability to heal itself to rebuild bone and muscle tissue and could help reduce the need for the often painful procedures of current methods.
“The sound waves cut the treatment time usually required to get stem cells to begin to turn into bone cells by several days,” explained Dr. Amy Gelmi, a Vice-Chancellor’s Research Fellow at RMIT and co-lead author of the study, in a statement.
“This method also doesn’t require any special ‘bone-inducing’ drugs and it’s very easy to apply to the stem cells. Our study found this new approach has strong potential to be used for treating the stem cells before we either coat them onto an implant or inject them directly into the body for tissue engineering” Gelmi added.
Up until now, the experimental processes to change adult stem cells into bone cells were both complicated and expensive, making them difficult to adopt to clinical applications.
The study of RMIT researchers showed that the stem cells treated with high-frequency sound waves, which were generated on a low-cost microchip device also developed by RMIT, turned into bone cells in a quick and efficient manner. The treatment worked on various types of cells, including far-less-painfully extracted fat-derived stem cells.
During the process, the small, scalable device delivers rapid high-frequency bursts to the targeted stem cells. The tests performed on adult patients showed that five treatments of ten minutes a day trigger the differentiation of stem cells into bone cells.
The next stage of the research will be investigating methods to upscale the platform and develop a bioreactor that can drive stem cells into bone cells in large quantities.
Stem cell fate can be directed through the application of various external physical stimuli, enabling a controlled approach to targeted differentiation. Studies involving the use of dynamic mechanical cues driven by vibrational excitation to date have, however, been limited to low frequency (Hz to kHz) forcing over extended durations (typically continuous treatment for >7 days). Contrary to previous assertions that there is little benefit in applying frequencies beyond 1 kHz, we show here that high frequency MHz-order mechanostimulation in the form of nanoscale amplitude surface reflected bulk waves are capable of triggering differentiation of human mesenchymal stem cells from various donor sources toward an osteoblast lineage, with early, short time stimuli inducing long-term osteogenic commitment. More specifically, rapid treatments (10 min daily over 5 days) of the high frequency (10 MHz) mechanostimulation are shown to trigger significant upregulation in early osteogenic markers (RUNX2, COL1A1) and sustained increase in late markers (osteocalcin, osteopontin) through a mechanistic pathway involving piezo channel activation and Rho-associated protein kinase signaling. Given the miniaturizability and low cost of the devices, the possibility for upscaling the platform toward practical bioreactors, to address a pressing need for more efficient stem cell differentiation technologies in the pursuit of translatable regenerative medicine strategies, is ensivaged.