Matrix interactions modulate neurotrophin-mediated neurite outgrowth and pathfinding  

作　　者：Christopher M.Madl Sarah C.Heilshorn 

机构地区：[1]Department of Bioengineering,Stanford University [2]Department of Materials Science and Engineering,Stanford University

出　　处：《Neural Regeneration Research》2015年第4期514-517,共4页中国神经再生研究（英文版）

基　　金：supported by the National Institutes of Health(1DP2-OD006477,R01-DK085720,R21-AR062359-01);the National Science Foundation(DMR-0846363)

摘　　要：Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathifnding; however, the interplay between these two factors is less studied. While previous work has shown that the biochemical identity of the matrix can alter the outgrowth of neurites in response to neurotrophins, the importance of the concentration of cell-adhesive ligands is unknown. Using engineered elastin-like protein matrices, we recently demonstrated a synergistic effect between matrix-bound cell-adhesive ligand density and soluble nerve growth factor treat-ment on neurite outgrowth from dorsal root ganglia. This synergism was mediated by Schwann cell-neurite contact through L1CAM. Cell-adhesive ligand density was also shown to alter the pathifnding behavior of dorsal root ganglion neurites in response to a gradient of nerve growth factor. While more cell-adhesive matrices promoted neurite outgrowth, less cell-adhesive ma-trices promoted more faithful neurite pathifnding. These studies emphasize the importance of considering both matrix biochemistry and neurotrophic factors when designing biomaterials for peripheral nerve regeneration.Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathifnding; however, the interplay between these two factors is less studied. While previous work has shown that the biochemical identity of the matrix can alter the outgrowth of neurites in response to neurotrophins, the importance of the concentration of cell-adhesive ligands is unknown. Using engineered elastin-like protein matrices, we recently demonstrated a synergistic effect between matrix-bound cell-adhesive ligand density and soluble nerve growth factor treat-ment on neurite outgrowth from dorsal root ganglia. This synergism was mediated by Schwann cell-neurite contact through L1CAM. Cell-adhesive ligand density was also shown to alter the pathifnding behavior of dorsal root ganglion neurites in response to a gradient of nerve growth factor. While more cell-adhesive matrices promoted neurite outgrowth, less cell-adhesive ma-trices promoted more faithful neurite pathifnding. These studies emphasize the importance of considering both matrix biochemistry and neurotrophic factors when designing biomaterials for peripheral nerve regeneration.

关 键 词：neurotrophic factors cell-adhesive ligands dorsal root ganglia L1CAM nerve growth factor biomaterials elastin-like proteins 

分 类 号：R338[医药卫生—人体生理学]