Self-assembling peptides optimize the post-traumatic milieu and synergistically enhance the effects of neural stem cell therapy after cervical spinal cord injury

Acta Biomater. 2016 Sep 15;42:77-89. doi: 10.1016/j.actbio.2016.06.016. Epub 2016 Jun 11.

Abstract

Introduction: The hostile environment after spinal cord injury (SCI) can compromise effects of regenerative therapies. We hypothesized that optimizing the post-traumatic environment with QL6 self-assembling peptides (SAPs) before neural precursor cell (NPC) transplantation would improve cell survival, differentiation and functional recovery.

Methods: A total of 90 Wistar rats received a clip-compression SCI at C7. Within each of two study arms, animals were randomized into 5 groups (NPC, SAP, NPC+SAP, vehicle, and sham). SAPs and NPCs were injected into the spinal cord 1day and 14days post-injury, respectively. Animals received growth factors over 7days and were immunosuppressed. Rats were sacrificed at 4weeks and sections of the cervical spinal cord prepared for immunohistochemistry (first study arm). Neurological function was assessed weekly for 8weeks using a battery of behavioral tests. Nine weeks post-SCI, the corticospinal tract was assessed using fiber-tracking (second arm).

Results: SAP-treated animals had significantly more surviving NPCs which showed increased differentiation to neurons and oligodendrocytes compared to controls. SAPs alone or in combination with NPCs resulted in smaller intramedullary cysts and larger volume of preserved tissue compared to other groups. The combined treatment group showed reduced astrogliosis and chondroitin sulfate proteoglycan deposition. Synaptic connectivity was increased in the NPC and combined treatment groups. Corticospinal tract preservation and behavioral outcomes improved with combinatorial treatment.

Conclusion: Injecting SAPs after SCI enhances subsequent NPC survival, integration and differentiation and improves functional recovery.

Statement of significance: The hostile environment after spinal cord injury (SCI) can compromise effects of regenerative therapies. We hypothesized that improving this environment with self-assembling peptides (SAPs) before neural precursor cell (NPC) transplantation would support their beneficial effects. SAPs assemble once injected, providing a supportive scaffold for repair and regeneration. We investigated this in a rat model of spinal cord injury. More NPCs survived in SAP-treated animals and these showed increased differentiation compared to controls. SAPS alone or in combination with NPCs resulted in smaller cysts and larger volume of preserved tissue with the combined treatment also reducing scarring and improving behavioral outcomes. Overall, injection of SAPs was shown to improve the efficacy of NPC treatment, a promising finding for those with SCIs.

Keywords: Cervical spinal cord injury; Functional recovery; Neural precursor cells; Self-assembling peptides; Tissue-preservation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Biotin / analogs & derivatives
  • Biotin / metabolism
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cervical Cord / drug effects
  • Cervical Cord / pathology*
  • Cervical Cord / physiopathology
  • Choline O-Acetyltransferase / metabolism
  • Cicatrix / complications
  • Cicatrix / pathology
  • Dextrans / metabolism
  • Female
  • Gliosis / complications
  • Gliosis / pathology
  • Hyperalgesia / complications
  • Hyperalgesia / physiopathology
  • Hyperalgesia / therapy
  • Microscopy, Fluorescence
  • Motor Neurons / drug effects
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / transplantation*
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Pyramidal Tracts / drug effects
  • Pyramidal Tracts / pathology
  • Rats, Wistar
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Stem Cell Transplantation*
  • Synapses / drug effects
  • Synapses / pathology
  • Wounds and Injuries / complications
  • Wounds and Injuries / drug therapy*
  • Wounds and Injuries / physiopathology

Substances

  • Dextrans
  • Peptides
  • biotinylated dextran amine
  • Biotin
  • Choline O-Acetyltransferase

Grant support