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Title: Biological and mechanical interplay at the macro- and microscales modulates the cell-niche fate
Authors: Sarig, Udi
Sarig, Hadar
Gora, Aleksander
Krishnamoorthi, Muthu Kumar
Au-Yeung, Gigi Chi Ting
de-Berardinis, Elio
Chaw, Su Yin
Mhaisalkar, Priyadarshini
Bogireddi, Hanumakumar
Ramakrishna, Seeram
Boey, Freddy Yin Chiang
Venkatraman, Subbu S.
Machluf, Marcelle
Keywords: Human Umbilical Vein Endothelial Cells (HUVECs)
Cell-niche Interactions
Issue Date: 2018
Source: Sarig, U., Sarig, H., Gora, A., Krishnamoorthi, M. K., Au-Yeung, G. C. T., de-Berardinis, E., et al. (2018). Biological and mechanical interplay at the macro- and microscales modulates the cell-niche fate. Scientific Reports, 8(1), 3937-.
Series/Report no.: Scientific Reports
Abstract: Tissue development, regeneration, or de-novo tissue engineering in-vitro, are based on reciprocal cell-niche interactions. Early tissue formation mechanisms, however, remain largely unknown given complex in-vivo multifactoriality, and limited tools to effectively characterize and correlate specific micro-scaled bio-mechanical interplay. We developed a unique model system, based on decellularized porcine cardiac extracellular matrices (pcECMs)—as representative natural soft-tissue biomaterial—to study a spectrum of common cell–niche interactions. Model monocultures and 1:1 co-cultures on the pcECM of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) were mechano-biologically characterized using macro- (Instron), and micro- (AFM) mechanical testing, histology, SEM and molecular biology aspects using RT-PCR arrays. The obtained data was analyzed using developed statistics, principal component and gene-set analyses tools. Our results indicated biomechanical cell-type dependency, bi-modal elasticity distributions at the micron cell-ECM interaction level, and corresponding differing gene expression profiles. We further show that hMSCs remodel the ECM, HUVECs enable ECM tissue-specific recognition, and their co-cultures synergistically contribute to tissue integration—mimicking conserved developmental pathways. We also suggest novel quantifiable measures as indicators of tissue assembly and integration. This work may benefit basic and translational research in materials science, developmental biology, tissue engineering, regenerative medicine and cancer biomechanics.
ISSN: 2045-2322
DOI: 10.1038/s41598-018-21860-6
Rights: © 2018 The Author(s) (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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