A prevascularized nerve conduit based on a stem cell sheet effectively promotes the repair of transected spinal cord injury

Acta Biomater. 2020 Jan 1;101:304-313. doi: 10.1016/j.actbio.2019.10.042. Epub 2019 Oct 31.

Abstract

Spinal cord injury (SCI) can result in severe loss of motor and sensory function caused by ischemia and hypoxia, which are the key limiting factors of SCI rehabilitation. Vascularization is considered an effective way to resolve the issues of ischemia and hypoxia. In this regard, we first fabricated prevascularized nerve conduits (PNC) based on the prevascularized stem cell sheet and evaluated their repair effects by implanting them into transected SCI rats. A better healing effect was presented in the PNC group than in the control group and the nonprevascularized nerve conduit (NPNC) group as shown in H&E staining and the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale assessment. In addition, the expression of β-III tubulin (Tuj-1) in the PNC group was higher than that in the control group and the NPNC group because of the introduction of MSCs. Conversely, the expression of the glial fibrillary acidic protein (GFAP) in both experimental groups was lower than that in the control group because of the inhibitory effect of MSCs on glial scar formation. Taken together, the introduction of prevascularization into the neuron conduit was an effective solution for improving the condition of ischemia and hypoxia, inhibiting glial scar formation, and promoting the healing of SCI, which implied that the PNC may be a potential alternative material to biomaterials for SCI rehabilitation. STATEMENT OF SIGNIFICANCE: 1. Prevascularized stem cell sheet was first used to repair spinal cord injury (SCI). 2. Prevascularized stem cell sheet use can effectively resolve the challenges faced during SCI, including ischemia and hypoxia and the limited regenerative ability of the remained neurons. 3. Prevascularized stem cell sheet was found to accelerate the healing of SCI as compared to those in the control group and the pure stem cell sheet group. 4. The introduction of stem cells can effectively inhibit the formation of a glial scar.

Keywords: Cell sheet; Prevascularization; Spinal cord injury; Stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / pathology
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Neovascularization, Physiologic*
  • Nerve Regeneration*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Rabbits
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / therapy*

Substances

  • Glial Fibrillary Acidic Protein
  • Platelet Endothelial Cell Adhesion Molecule-1