Engineering polysialic acid on Schwann cells using polysialyltransferase gene transfer or purified enzyme exposure for spinal cord injury transplantation

Neurosci Lett. 2021 Mar 23:748:135690. doi: 10.1016/j.neulet.2021.135690. Epub 2021 Feb 1.

Abstract

Polysialic acid (PolySia) is a critical post-translational modification on the neural cell adhesion molecule (NCAM, a.k.a., CD56), important for cell migration and axon growth during nervous system development, plasticity and repair. PolySia induction on Schwann cells (SCs) enhances their migration, axon growth support and ability to improve functional recovery after spinal cord injury (SCI) transplantation. In the current investigation two methods of PolySia induction on SCs, lentiviral vector transduction of the mouse polysialytransferase gene ST8SIA4 (LV-PST) or enzymatic engineering with a recombinant bacterial PST (PSTNm), were examined comparatively for their effects on PolySia induction, SC migration, the innate immune response and axon growth after acute SCI. PSTNm produced significant PolySia induction and a greater diversity of surface molecule polysialylation on SCs as evidenced by immunoblot. In the scratch wound assay, PSTNm was superior to LV-PST in the promotion of SC migration and gap closure. At 24 h after SCI transplantation, PolySia induction on SCs was most pronounced with LV-PST. Co-delivery of PSTNm with SCs, but not transient cell exposure, led to broader induction of PolySia within the injured spinal cord due to polysialylation upon both host cells and transplanted SCs. The innate immune response after SCI, measured by CD68 immunoreactivity, was similar among PolySia induction methods. LV-PST or PSTNm co-delivery with SCs provided a similar enhancement of SC migration and axon growth support above that of unmodified SCs. These studies demonstrate that LV-PST and PSTNm provide comparable acute effects on SC polysialation, the immune response and neurorepair after SCI.

Keywords: Axon growth; Cell migration; Polysialic acid; Polysialytransferase; Schwann cell transplantation; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Disease Models, Animal
  • Mice
  • Neural Cell Adhesion Molecules
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Schwann Cells / drug effects*
  • Schwann Cells / metabolism
  • Sialic Acids / pharmacology*
  • Sialyltransferases / drug effects*
  • Sialyltransferases / genetics
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / physiopathology

Substances

  • Neural Cell Adhesion Molecules
  • Sialic Acids
  • polysialic acid
  • Sialyltransferases