Directed nerve outgrowth is enhanced by engineered glial substrates.
In the present study, the influence of astrocyte alignment on the direction and length of regenerating neurites was examined in vitro. Astrocytes were experimentally manipulated by different approaches to create longitudinally aligned monolayers. When cultured on the aligned monolayers, dorsal root ganglion neurites grew parallel to the long axis of the aligned astrocytes and were significantly longer than controls. Engineered monolayers expressed linear arrays of fibronectin, laminin, neural cell adhesion molecule, and chondroitin sulfate proteoglycan that were organized parallel to one another, suggesting that a particular spatial arrangement of these molecules on the astrocyte surface may be necessary to direct nerve regeneration in vivo. In contrast, no bias in directional outgrowth was observed for neurites growing on unorganized monolayers. The results suggest that altering the organization of astrocytes and their scar-associated matrix at the lesion site may be used to influence the direction and the length of adjacent regenerating axons in the damaged brain and spinal cord.
Biran
Roy
R
The Keck Center for Tissue Engineering, Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
Noble
Mark D
MD
Tresco
Patrick A
PA
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology; D003470:Culture Media; D005353:Fibronectins / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000166:cytology; D007091:Image Processing, Computer-Assisted; D007797:Laminin / Q000494:pharmacology; D009416:Nerve Regeneration / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000494:pharmacology; D016501:Neurites / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley
D011508:Chondroitin Sulfate Proteoglycans; D003470:Culture Media; D005353:Fibronectins; D007797:Laminin; D019006:Neural Cell Adhesion Molecules