"Nanokicking" Stem Cells Offers Cheaper And Easier Way To Grow New Bone

Researchers in Scotland have developed a new method that coaxes stem cells into growing new bone by "nanokicking" them 1,000 times per second. They suggest the technology is cheaper and easier to implement than the current methods and opens the door to new ways of treating bone conditions like stress fractures, spinal traumas and osteoporosis.

Matt Dalby from the Centre for Cell Engineering at the University of Glasgow, and colleagues, write about their work in a study that was published recently in the journal ACS Nano.

In a statement released this week, Dalby says their new method offers a simple way of "converting adult stem cells from the bone marrow into bone-making cells on a large scale without the use of cocktails of chemicals or recourse to challenging and complex engineering".

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that occur naturally in the body and have the potential to form cells that make up certain tissue types such as bone, cartilage, ligament, tendon and muscle.

Scientists have found it is possible to grow these tissue types in the lab by isolating MSCs and culturing them in an environment that simulates that which occurs naturally in the human body.

But current methods of coaxing the stem cells to differentiate are notoriously problematic and require expensive and highly engineered materials or complex chemical cocktails.


Dalby and colleagues have developed a new technique for coaxing MSCs that uses "nanoscale sinusoidal mechanotransductive protocols", a term they have shortened to "nanokicking".

Nanokicking replicates a vibration that occurs in the membranes of bone cells when they stick together to form new bone naturally in the body.

The vibration, which has a frequency of 1,000 times per second, is thought to promote bone formation by encouraging signals between bone cells.

In the lab, the stem cells are about 5-30 nanometers apart when they receive their "nanokicking" at 1,000 times per second.

An Unlikely Match: Cell Biologists and Astrophysicists

To deliver the nanokick precisely and at the right frequency, the researchers use an incredibly precise technique called laser interferometry, which is more commonly seen in the astrophysic lab to detect tiny ripples made by gravitational waves in space-time.

In a remarkable example of collaboration between widely different disciplines, Dalby and fellow cell engineer Adam Curtis, also of the University of Glasgow, worked with astrophysicist Stuart Reid from the University of the West of Scotland's Thin Film Centre to adapt the laser interferometer for the study.

Reid explains:

"Linking stem cell research with expertise from the field of gravitational wave astronomy, where we have developed instrumentation that can measure length changes almost million times smaller than the diameter of a proton, have enabled this unique research field to emerge."

Dalby adds:

"Multidisciplinary research is tricky as researchers need to learn new scientific languages, however, this collaboration between cell biologists and astrophysicists - an unlikely pairing - has yielded new insight as to how bone stem cells work."

Next Steps: Collaboration with Rehabilitation Engineers and Working with Patients

The researchers hope their new technique will herald a fundamental change in the way we grow new bone.

They are now planning to work with rehabilitation engineers in the Queen Elizabeth National Spinal Injuries Unit (Southern General Hospital, Glasgow) to help patients with spinal injuries.

The vibration therapy techniques that Dalby and colleagues have developed in the lab now have to be scaled up and tested in patients to assess how well they stimulate new bone growth in whole bones.

In their study conclusions they don't appear to see the upscaling as a huge problem:

" It is easy to envisage such stimulation protocols being up-scaled to form large-scale osteoblast bioreactors as standard cell culture plates and incubators are used in the protocol."

"We look forwards to working with the rehabilitation engineers; this will provide us with new challenges, but challenges that we welcome," says Dalby.

In June 2012, US scientists writing in Stem Cells Translational Medicine, describe how they found a way to grow new bone using fresh, purified mesenchymal stem cells from fat tissue.


Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction

It is likely that mesenchymal stem cells will find use in many autologous regenerative therapies. However, our ability to control cell stem growth and differentiation is presently limited, and this is a major hurdle to the clinical use of these multipotent cells especially when considering the desire not to use soluble factors or complex media formulations in culture. Also, the large number of cells required to be clinically useful is currently a hurdle to using materials-based (stiffness, chemistry, nanotopography, etc.) culture substrates. Here we give a first demonstration of using nanoscale sinusoidal mechanotransductive protocols (10–14 nm displacements at 1 kHz frequency), “nanokicking”, to promote osteoblastogenesis in human mesenchymal stem cell cultures. On the basis of application of the reverse piezo effect, we use interferometry to develop the optimal stem cell stimulation conditions, allowing delivery of nanoscale cues across the entire surface of the Petri dishes used. A combination of immunofluorescence, PCR, and microarray has then been used to demonstrate osteoblastogenesis, and the arrays implicate RhoA as central to osteoblastic differentiation in agreement with materials-based strategies. We validate this with pharmacological inhibition of RhoA kinase. It is easy to envisage such stimulation protocols being up-scaled to form large-scale osteoblast bioreactors as standard cell culture plates and incubators are used in the protocol.

"Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction"
; Habib Nikukar, Stuart Reid, P. Monica Tsimbouri, Mathis O. Riehle, Adam S. G. Curtis, and Matthew J. Dalby; ACS Nano2013 7 (3), 2758-2767; DOI: 10.1021/nn400202j; Link to Abstract. (pubs.acs.org/doi/abs/10.1021/nn400202j)
Additional source: University of Glasgow. (gla.ac.uk/news/headline_274263_en.html)