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Biomaterials. 2013 Mar;34(8):1921-8. doi: 10.1016/j.biomaterials.2012.11.063. Epub 2012 Dec 14.

Maintenance of the self-renewal properties of neural progenitor cells cultured in three-dimensional collagen scaffolds by the REDD1-mTOR signal pathway.

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  • 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

Abstract

Three-dimensional (3-D) culture, compared with traditional two-dimensional (2-D) cell culture, can provide physical signals and 3-D matrix close to the in vivo microenvironments. Here, sponge-like collagen scaffolds were used to assess how 3-D culture would affect the differentiation and self-renewal of neural progenitor cells (NPCs). Cultured in differentiation medium without growth factors, cells in 3-D collagen scaffolds yielded much higher clone formation efficiency and expressed less neuron marker, TUJ1, compared with cells cultured on 2-D plates. mTOR inactivation was identified and showed to supported the self-renewal of NPCs in 3-D culture. At the same time, REDD1 was highly expressed in cells cultured in 3-D conditions, which blocks the activity of mTOR. Moreover, knocking-down REDD1 induced the differentiation of NPCs in 3-D collagen scaffolds. These results indicated that mTOR inactivation by REDD1 mediated the self-renewal regulation of NPCs in 3-D cultures. Thus, 3-D collagen scaffolds maintained self-renewal properties of NPCs, and the inhibitory regulator of mTOR (such as REDD1) played an important role in the regulation of self-renewal and differentiation of NPCs.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:
23246064
[PubMed - indexed for MEDLINE]
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