Campus Units

Genetics, Development and Cell Biology, Biomedical Sciences, Chemical and Biological Engineering, Neuroscience

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

11-2009

Journal or Book Title

Journal of Biomedical Materials Research Part A

Volume

91A

Issue

2

First Page

575

Last Page

585

DOI

10.1002/jbm.a.32242

Abstract

Rat adult hippocampal progenitor cells (AHPCs) are self-renewing, multipotent neural progenitors that have the ability to differentiate into neurons and glia. Previously, we demonstrated that coculture of AHPCs with postnatal day two, type 1 cortical astrocytes on laminin-coated micropatterned polymer substrates facilitates selective neuronal differentiation of the AHPCs 1. Under this condition, multi-dimensional cell-cell and/or cell-extracellular matrix interactions, as well as possible soluble factors released from astrocytes provided spatial and temporal control selectively enhancing neuronal differentiation and neurite alignment on topographically different regions of the same substrate. To investigate the potential role of astrocyte-derived soluble factors as cues involved in neuronal differentiation, a non-contact co-culture system was used. Under control conditions, approximately 14% of the AHPCs were immunoreactive (IR) for the neuronal marker, class III β-tubulin (TUJ1-IR). When co-cultured in physical contact with astrocytes, neuronal differentiation increased significantly to about 25%, consistent with our previous results. Moreover, under non-contact co-culture conditions using Transwell insert cultures, neuronal differentiation was dramatically increased to approximately 64%. Furthermore, neurite outgrowth from neuronal cell bodies was considerably greater on the patterned substrate, compared to the non-patterned planar substrate under non-contact co-culture conditions. Taken together, our results demonstrate that astrocyte-derived soluble factors provide cues for specific neuronal differentiation of AHPCs cultured on micropatterned substrates. In addition, a suppressive influence on neuronal differentiation appears to be mediated by contact with co-cultured astrocytes. These results provide important insights into mechanisms for controlling neural progenitor/stem cell differentiation and facilitate development of strategies for CNS repair.

Comments

This is the peer reviewed version of the following article: Oh, J., Recknor, J. B., Recknor, J. C., Mallapragada, S. K. and Sakaguchi, D. S. (2009), Soluble factors from neocortical astrocytes enhance neuronal differentiation of neural progenitor cells from adult rat hippocampus on micropatterned polymer substrates. J. Biomed. Mater. Res., 91A: 575–585, which has been published in final form at doi:10.1002/jbm.a.32242. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

Copyright Owner

Wiley Periodicals, Inc.

Language

en

File Format

application/pdf