Human mesenchymal stromal cells in adhesion to cell-derived extracellular matrix and titanium: Comparative kinome profile analysis |
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| Authors: | Marta Baroncelli Gwenny M. Fuhler Jeroen van de Peppel Willian F. Zambuzzi Johannes P. van Leeuwen Bram C. J. van der Eerden Maikel P. Peppelenbosch |
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| Affiliation: | 1. Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;2. Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands It is Baroncelli and Fuhler contributed equally to this work (first shared). van der Eerden and Peppelenbosch contributed equally to this work (shared last).;3. Laboratorio de Bioensaios e Dinâmica Celular, Departamento de Quimica e Bioquimica, Instituto de Biociências, Universidade Estadual Paulista-UNESP, São Paulo, Brazil |
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| Abstract: | The extracellular matrix (ECM) physically supports cells and influences stem cell behaviour, modulating kinase-mediated signalling cascades. Cell-derived ECMs have emerged in bone regeneration as they reproduce physiological tissue-architecture and ameliorate mesenchymal stromal cell (MSC) properties. Titanium scaffolds show good mechanical properties, facilitate cell adhesion, and have been routinely used for bone tissue engineering (BTE). We analyzed the kinomic signature of human MSCs in adhesion to an osteopromotive osteoblast-derived ECM, and compared it to MSCs on titanium. PamChip kinase-array analysis revealed 63 phosphorylated peptides on ECM and 59 on titanium, with MSCs on ECM exhibiting significantly higher kinase activity than on titanium. MSCs on the two substrates showed overlapping kinome profiles, with activation of similar signalling pathways (FAK, ERK, and PI3K signalling). Inhibition of PI3K signalling in cells significantly reduced adhesion to ECM and increased the number of nonadherent cells on both substrates. In summary, this study comprehensively characterized the kinase activity in MSCs on cell-derived ECM and titanium, highlighting the role of PI3K signalling in kinomic changes regulating osteoblast viability and adhesion. Kinome profile analysis represents a powerful tool to select pathways to better understand cell behaviour. Osteoblast-derived ECM could be further investigated as titanium scaffold-coating to improve BTE. |
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| Keywords: | cell adhesion extracellular matrix kinome profiling osteoblasts titanium |
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