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The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells

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posted on 11.05.2021, 16:01 by Tom Hodgkinson, P Monica Tsimbouri, Virginia Llopis-Hernandez, Paul Campsie, David Scurr, Peter G Childs, David Phillips, Sam Donnelly, Julia A Wells, Fergal O'Brien, Manuel Salmeron-Sanchez, Karl Burgess, Morgan Alexander, Massimo Vassalli, Richard OC Oreffo, Stuart Reid, David J France, Matthew J Dalby
Bioactive metabolites have wide-ranging biological activities and are a potential source of future research and therapeutic tools. Here, we use nanovibrational stimulation to induce osteogenic differentiation of mesenchymal stem cells, in the absence of off-target, nonosteogenic differentiation. We show that this differentiation method, which does not rely on the addition of exogenous growth factors to culture media, provides an artifact-free approach to identifying bioactive metabolites that specifically and potently induce osteogenesis. We first identify a highly specific metabolite, cholesterol sulfate, an endogenous steroid. Next, a screen of other small molecules with a similar steroid scaffold identified fludrocortisone acetate with both specific and highly potent osteogenic-inducing activity. Further, we implicate cytoskeletal contractility as a measure of osteogenic potency and cell stiffness as a measure of specificity. These findings demonstrate that physical principles can be used to identify bioactive metabolites and then enable optimization of metabolite potency can be optimized by examining structure-function relationships.

Funding

BBSRC project BB/P00220X/1

EPSRC projects EP/P001114/1

EP/N013905/1

European Research Council Advanced Grant agreement no. 788753

The EPSRC Strategic Equipment grant “3D OrbiSIMS: Label free chemical imaging of materials, cells and tissues” (grant no. EP/P029868/1)

UK Regenerative Medicine Platform Acellular/SmartMaterials–3D Architecture (MR/R015651/1)

History

Associated research data files

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/7/9/eabb7921/DC1

Comments

The original article is available at https://advances.sciencemag.org

Published Citation

Hodgkinson T, Tsimbouri PM, Llopis-Hernandez V, Campsie P, Scurr D, Childs PG, Phillips D, Donnelly S, Wells JA, O'Brien FJ, Salmeron-Sanchez M, Burgess K, Alexander M, Vassalli M, Oreffo ROC, Reid S, France DJ, Dalby MJ. The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells. Science Advances. 2021;7(9):eabb7921.

Publication Date

26 February 2021

PubMed ID

33637520

Department/Unit

  • Anatomy and Regenerative Medicine
  • RCSI Tissue Engineering Group (TERG)

Research Area

  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation

Publisher

American Association for the Advancement of Science (AAAS)

Version

  • Published Version (Version of Record)