Biological and mechanical interplay at the Macro- and Microscales Modulates the Cell-Niche Fate

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...

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Published in:Scientific reports 2018-03, Vol.8 (1), p.3937-16, Article 3937
Main 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
Format: Article
Language:English
Subjects:
Biomaterials
Cancer
Data processing
Developmental biology
Endothelial cells
Extracellular matrix
Gene expression
Heart diseases
Mechanical properties
Mesenchyme
Mimicry
Polymerase chain reaction
Regenerative medicine
Stem cell transplantation
Stem cells
Tissue engineering
Umbilical vein
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Summary: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
2045-2322
DOI:10.1038/s41598-018-21860-6