Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury.
Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.
Tysseling-Mattiace
Vicki M
VM
Department of Neurology, Northwestern University, Chicago, Illinois 60611, USA.
Sahni
Vibhu
V
Niece
Krista L
KL
Birch
Derin
D
Czeisler
Catherine
C
Fehlings
Michael G
MG
Stupp
Samuel I
SI
Kessler
John A
JA
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002921:Cicatrix / Q000188:drug therapy; D003952:Diagnostic Imaging / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy; D007797:Laminin / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D009046:Motor Neurons / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D010446:Peptide Fragments; C083321:isoleucyl-lysyl-valyl-alanyl-valine; D053148:Caspase 3