Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 43, Issue 2, Pages 177-187Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2009.10.008
Keywords
Fibrotic scar; Fibroblast; Astrocyte; TGF-beta; Chondroitin sulfate; Neurite outgrowth
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Funding
- Ministry of Education, Science, Sports and Culture of Japan [20500318]
- Grants-in-Aid for Scientific Research [20500318] Funding Source: KAKEN
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After central nervous system (CNS) injury, meningeal fibroblasts migrate in the lesion center to form a fibrotic scar which is surrounded by end feet of reactive astrocytes. The fibrotic scar expresses various axonal growth-inhibitory molecules and creates a major impediment for axonal regeneration. We developed an in vitro model of the scar using coculture of cerebral astrocytes and meningeal fibroblasts by adding transforming growth factor-beta 1 (TGF-beta 1), a potent fibrogenic factor. Addition of TGF-beta 1 to this coculture resulted in enhanced proliferation of fibroblasts and the formation of cell clusters which consisted of fibroblasts inside and surrounded by astrocytes. The cell cluster in culture densely accumulated the extracellular matrix molecules and axonal growth-inhibitory molecules similar to the fibrotic scar, and remarkably inhibited the neurite outgrowth of cerebellar neurons. Therefore, this culture system can be available to analyze the inhibitory property in the lesion site of CNS. (C) 2009 Elsevier Inc. All rights reserved.
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