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

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Silvia A Ferreira, Meghna Suresh Motwani, Peter A. Faull, Alexis Jane Seymour, Tong Yu, Marjan Enayati, Dheraj Kumar Taheem, Ewa Monika Kania, Oommen P Oommen, Tarek Ahmed, Sandra Loaiza, Katarzyna Parzych, Francesco Dazzi, H. W. Auner, Oommen P. Varghese, Frederic Festy, Agamemnon Emil Grigoriadis, Ambrosius P. Snijders, Laurent Bozec, Eileen Deirdre Gentleman

Original languageEnglish
Article number4049
Number of pages12
JournalNature Communications
Volume9
Issue number1
Early online date3 Oct 2018
DOIs
Accepted/In press10 Aug 2018
E-pub ahead of print3 Oct 2018
Published3 Oct 2018

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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 play 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.

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