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. SnijdersLaurent Bozec, Eileen Gentleman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

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.

Original languageEnglish (US)
Article number4049
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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