Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction

Habib Nikukar, Stuart Reid, P. Monica Tsimbouri, Mathis O. Riehle, Adam S. G. Curtis, Matthew J. Dalby

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)2758–2767
JournalACS Nano
Volume7
Issue number3
DOIs
Publication statusPublished - 2013

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osteogenesis
stem cells
Stem cells
stimulation
Cell culture
bioreactors
osteoblasts
parabolic reflectors
Osteoblasts
cues
Microarrays
Bioreactors
cells
Interferometry
therapy
stiffness
delivery
interferometry
Phosphotransferases
Demonstrations

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Nikukar, H., Reid, S., Tsimbouri, P. M., Riehle, M. O., Curtis, A. S. G., & Dalby, M. J. (2013). Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction. ACS Nano, 7(3), 2758–2767. https://doi.org/10.1021/nn400202j
Nikukar, Habib ; Reid, Stuart ; Tsimbouri, P. Monica ; Riehle, Mathis O. ; Curtis, Adam S. G. ; Dalby, Matthew J. / Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction. In: ACS Nano. 2013 ; Vol. 7, No. 3. pp. 2758–2767.
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Nikukar, H, Reid, S, Tsimbouri, PM, Riehle, MO, Curtis, ASG & Dalby, MJ 2013, 'Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction' ACS Nano, vol. 7, no. 3, pp. 2758–2767. https://doi.org/10.1021/nn400202j

Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction. / Nikukar, Habib; Reid, Stuart; Tsimbouri, P. Monica; Riehle, Mathis O.; Curtis, Adam S. G.; Dalby, Matthew J.

In: ACS Nano, Vol. 7, No. 3, 2013, p. 2758–2767.

Research output: Contribution to journalArticle

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AU - Nikukar, Habib

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Nikukar H, Reid S, Tsimbouri PM, Riehle MO, Curtis ASG, Dalby MJ. Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction. ACS Nano. 2013;7(3):2758–2767. https://doi.org/10.1021/nn400202j