Bi-directional cell-pericellular matrix interactions direct stem cell fate

Silvia A. Ferreira, Meghna S. Motwani, Peter A. Faull, Alexis J. Seymour, Tracy T. L. Yu, Marjan Enayati, Dheraj K. Taheem, Christoph Salzlechner, Tabasom Haghighi, Ewa M. Kania, Oommen P. Oommen, Tarek Ahmed, Sandra Loaiza, Katarzyna Parzych, Francesco Dazzi, Oommen P. Varghese, Frederic Festy, Agamemnon E. Grigoriadis, Holger W. Auner, Ambrosius P. Snijders, Laurent Bozec and Eileen Gentleman ()
Additional contact information
Silvia A. Ferreira: King’s College London
Meghna S. Motwani: King’s College London
Peter A. Faull: The Francis Crick Institute
Alexis J. Seymour: King’s College London
Tracy T. L. Yu: King’s College London
Marjan Enayati: King’s College London
Dheraj K. Taheem: King’s College London
Christoph Salzlechner: King’s College London
Tabasom Haghighi: King’s College London
Ewa M. Kania: King’s College London
Oommen P. Oommen: Tampere University of Technology and BioMediTech Institute
Tarek Ahmed: University College London
Sandra Loaiza: Imperial College London
Katarzyna Parzych: Imperial College London
Francesco Dazzi: King’s College London
Oommen P. Varghese: Uppsala University
Frederic Festy: King’s College London
Agamemnon E. Grigoriadis: King’s College London
Holger W. Auner: Imperial College London
Ambrosius P. Snijders: The Francis Crick Institute
Laurent Bozec: University College London
Eileen Gentleman: King’s College London

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06183-4

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