Abstract

Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.

Details

Title
Bi-directional cell-pericellular matrix interactions direct stem cell fate
Author
Ferreira, Silvia A 1   VIAFID ORCID Logo  ; Motwani, Meghna S 1 ; Faull, Peter A 2 ; Seymour, Alexis J 1 ; Yu, Tracy T L 1 ; Enayati, Marjan 3 ; Taheem, Dheraj K 1 ; Salzlechner, Christoph 1 ; Haghighi, Tabasom 1 ; Kania, Ewa M 1 ; Oommen, Oommen P 4   VIAFID ORCID Logo  ; Ahmed, Tarek 5 ; Loaiza, Sandra 6 ; Parzych, Katarzyna 6 ; Dazzi, Francesco 7 ; Varghese, Oommen P 8 ; Festy, Frederic 9 ; Grigoriadis, Agamemnon E 1 ; Auner, Holger W 6   VIAFID ORCID Logo  ; Snijders, Ambrosius P 2   VIAFID ORCID Logo  ; Bozec, Laurent 10 ; Gentleman, Eileen 1   VIAFID ORCID Logo 

1  Centre for Craniofacial and Regenerative Biology, King’s College London, London, UK 
2  Protein Analysis and Proteomics Platform, The Francis Crick Institute, London, UK 
3  Centre for Craniofacial and Regenerative Biology, King’s College London, London, UK; Ludwig Boltzmann Cluster for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, Vienna, Austria 
4  Bioengineering and Nanomedicine Lab, Faculty of Biomedical Sciences and Engineering, Tampere University of Technology and BioMediTech Institute, Tampere, Finland 
5  Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, London, UK 
6  Cancer Cell Protein Metabolism Group, Department of Medicine, Imperial College London, London, UK 
7  Department of Haemato-Oncology, Rayne Institute, King’s College London, London, UK 
8  Department of Chemistry, Ångström Laboratory, Science for Life Laboratory, Uppsala University, Uppsala, Sweden 
9  Tissue Engineering and Biophotonics, King’s College London, London, UK 
10  Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, London, UK; Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Toronto, Canada 
Pages
1-12
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06183-4
ProQuest document ID
2116055007
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.