Notch-inducing hydrogels reveal a perivascular switch of mesenchymal stem cell fate

TY - JOUR

T1 - Notch-inducing hydrogels reveal a perivascular switch of mesenchymal stem cell fate

AU - Blache, Ulrich

AU - Vallmajo-Martin, Queralt

AU - Horton, Edward R.

AU - Guerrero, Julien

AU - Djonov, Valentin

AU - Scherberich, Arnaud

AU - Erler, Janine T.

AU - Martin, Ivan

AU - Snedeker, Jess G.

AU - Milleret, Vincent

AU - Ehrbar, Martin

PY - 2018

Y1 - 2018

N2 - The fate of mesenchymal stem cells (MSCs) in the perivascular niche, as well as factors controlling their fate, is poorly understood. Here, we study MSCs in the perivascular microenvironment of endothelial capillaries by modifying a synthetic 3D biomimetic poly(ethylene glycol) (PEG)-hydrogel system in vitro. We show that MSCs together with endothelial cells form micro-capillary networks specifically in soft PEG hydrogels. Transcriptome analysis of human MSCs isolated from engineered capillaries shows a prominent switch in extracellular matrix (ECM) production. We demonstrate that the ECM phenotypic switch of MSCs can be recapitulated in the absence of endothelial cells by functionalizing PEG hydrogels with the Notch-activator Jagged1. Moreover, transient culture of MSCs in Notch-inducing microenvironments reveals the reversibility of this ECM switch. These findings provide insight into the perivascular commitment of MSCs by use of engineered niche-mimicking synthetic hydrogels.

AB - The fate of mesenchymal stem cells (MSCs) in the perivascular niche, as well as factors controlling their fate, is poorly understood. Here, we study MSCs in the perivascular microenvironment of endothelial capillaries by modifying a synthetic 3D biomimetic poly(ethylene glycol) (PEG)-hydrogel system in vitro. We show that MSCs together with endothelial cells form micro-capillary networks specifically in soft PEG hydrogels. Transcriptome analysis of human MSCs isolated from engineered capillaries shows a prominent switch in extracellular matrix (ECM) production. We demonstrate that the ECM phenotypic switch of MSCs can be recapitulated in the absence of endothelial cells by functionalizing PEG hydrogels with the Notch-activator Jagged1. Moreover, transient culture of MSCs in Notch-inducing microenvironments reveals the reversibility of this ECM switch. These findings provide insight into the perivascular commitment of MSCs by use of engineered niche-mimicking synthetic hydrogels.

KW - extracellular matrix

KW - mesenchymal stem cell

KW - Notch signaling

KW - perivascular niche

KW - synthetic hydrogel

U2 - 10.15252/embr.201845964

DO - 10.15252/embr.201845964

M3 - Journal article

C2 - 29967223

AN - SCOPUS:85050821848

SN - 1469-221X

VL - 19

SP - 1

EP - 14

JO - EMBO Reports

JF - EMBO Reports

IS - 8

M1 - e45964

ER -