Maintenance of neural progenitor cell stemness in 3D hydrogels requires matrix remodelling.
Nat Mater
; 16(12): 1233-1242, 2017 12.
Article
in En
| MEDLINE
| ID: mdl-29115291
ABSTRACT
Neural progenitor cell (NPC) culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically relevant range of stiffness from â¼0.5 to 50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness. This requirement for degradation was independent of cytoskeletal tension generation and presentation of engineered adhesive ligands, instead relying on matrix remodelling to facilitate cadherin-mediated cell-cell contact and promote ß-catenin signalling. In two additional hydrogel systems, permitting NPC-mediated matrix remodelling proved to be a generalizable strategy for stemness maintenance in 3D. Our findings have identified matrix remodelling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Materials Testing
/
Signal Transduction
/
Cell Communication
/
Hydrogels
/
Extracellular Matrix
/
Neural Stem Cells
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nat Mater
Journal subject:
CIENCIA
/
QUIMICA
Year:
2017
Type:
Article
Affiliation country:
United States