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Substrate-dependent Wnt signaling in MSC differentiation within biomaterial-derived 3D spheroids

Paper ID Volume ID Publish Year Pages File Format Full-Text
6526 499 2013 14 PDF Available
Title
Substrate-dependent Wnt signaling in MSC differentiation within biomaterial-derived 3D spheroids
Abstract

A unique biomaterial-based system was developed to generate dynamic three-dimensional (3D) multicellular spheroids of mesenchymal stem cells (MSCs). MSCs were cultured on transparent membranes made of chitosan or those further grafted with hyaluronan (HA) in different densities. MSCs vigorously migrated and were self-assembled into highly mobile 3D spheroids with substrate-dependent upregulation of adhesion molecule N-cadherin. MSC spheroids showed increased expression of Wnt genes/proteins and substrate-dependent cell fate. The correlation of differentiation capacities with Wnt signaling and crosstalk with other pathways such as ERK1/2 or Smad2/3 were observed for MSC spheroids but not for the conventional 2D cultured cells. Wnt3a-mediated canonical Wnt signaling was more active for MSC spheroids derived on chitosan, which were prone to osteogenesis. Wnt5a-mediated non-canonical Wnt signaling was more active for MSC spheroids derived on HA-grafted chitosan, which were prone to chondrogenesis. In particular, the relative importance of Wnt5a-mediated non-canonical vs. Wnt3a-mediated canonical Wnt signals in determining the cell fate was controlled by the grafting density of HA on chitosan. Treatment with the inhibitor of canonical Wnt-associated signaling molecules suppressed the osteogenesis of MSC spheroids on chitosan. This study demonstrates that Wnt signaling of MSCs is distinct in 3D environment and is substrate-dependent. The convenient 3D platform may be used to examine the role of Wnt signaling in controlling MSC fate under different extracellular environments, and potentially applied to study stem cell behavior in regenerative medicine, normal development, and cancer.

Keywords
Mesenchymal stem cells (MSCs); Spheroids; Wnt signaling; Chitosan; Hyaluronan
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Substrate-dependent Wnt signaling in MSC differentiation within biomaterial-derived 3D spheroids
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 20, July 2013, Pages 4725–4738
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us